Single Cell Transcriptomics Trajectory and Molecular Convergence of Clinically Relevant Mutations in Brugada Syndrome
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00061.2021. Online ahead of print.ABSTRACTBrugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence of clinically relevant mutations and to identify developmental cardiac cell types that are associated with BrS etiology, we collected 733 mutations represented by 16 sodium, calcium, potassium channels, regulatory and structural genes related to BrS. Among the clinically relevant mutations, 266 are unique singletons and 88 mutations are recurrent. We observed an over representation of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Richa Tambi Reem Abdel Hameid Asma Bankapur Nasna Nassir Ghausia Begum Alawi Alsheikh-Ali Mohammed Uddin Bakhrom K Berdiev Source Type: research

Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00869.2020. Online ahead of print.ABSTRACTHigh levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. P...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Paulina Bryl-G órecka Kreema James Kristina Torngren Inger Haraldsson Li-Ming Gan Sara Svedlund Bj örn Olde Thomas Laurell Elmir Omerovic David Erlinge Source Type: research

No Evidence of Racial Disparities in Blood Pressure Salt Sensitivity When Potassium Intake Exceeds Levels Recommended in the US Dietary Guidelines
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00980.2020. Online ahead of print.ABSTRACTOn average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/d, black adults do not appear more sensitive than white adults to BP effects of short-term...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Theodore W Kurtz Stephen E DiCarlo Michal Pravenec R Curtis Morris Source Type: research

Ignoring a basic pathophysiological mechanism of heart failure progression will not make it go away
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00105.2021. Online ahead of print.ABSTRACTA link between heart failure (HF) and low thyroid hormone (TH) function has been known for over a century. Nonetheless, there is a general belief that TH treatment of HF patients may not be worth the risk. This is largely based on two clinical trials where heart patients were treated with excessive doses of TH analogs, not actual THs. Further complicating the issue is the fact that normalization of THs in non-cardiac patients can often be challenging. This issue is not going away as noted by a steady increase in TH-...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: A Martin Gerdes Michael A Portman Giorgio Iervasi Alessandro Pingitore David Kc Cooper Dimitri Novitzky Source Type: research

Role of arterial impairment in preeclampsia: should the paradigm shift?
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.01005.2020. Online ahead of print.ABSTRACTPreeclampsia is a worldwide pregnancy complication with serious short and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Maria M Pereira Juan Torrado Claudio Sosa Yanina Z ócalo Daniel Bia Source Type: research

Single Cell Transcriptomics Trajectory and Molecular Convergence of Clinically Relevant Mutations in Brugada Syndrome
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00061.2021. Online ahead of print.ABSTRACTBrugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence of clinically relevant mutations and to identify developmental cardiac cell types that are associated with BrS etiology, we collected 733 mutations represented by 16 sodium, calcium, potassium channels, regulatory and structural genes related to BrS. Among the clinically relevant mutations, 266 are unique singletons and 88 mutations are recurrent. We observed an over representation of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Richa Tambi Reem Abdel Hameid Asma Bankapur Nasna Nassir Ghausia Begum Alawi Alsheikh-Ali Mohammed Uddin Bakhrom K Berdiev Source Type: research

Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00869.2020. Online ahead of print.ABSTRACTHigh levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. P...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Paulina Bryl-G órecka Kreema James Kristina Torngren Inger Haraldsson Li-Ming Gan Sara Svedlund Bj örn Olde Thomas Laurell Elmir Omerovic David Erlinge Source Type: research

No Evidence of Racial Disparities in Blood Pressure Salt Sensitivity When Potassium Intake Exceeds Levels Recommended in the US Dietary Guidelines
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00980.2020. Online ahead of print.ABSTRACTOn average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/d, black adults do not appear more sensitive than white adults to BP effects of short-term...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Theodore W Kurtz Stephen E DiCarlo Michal Pravenec R Curtis Morris Source Type: research

Ignoring a basic pathophysiological mechanism of heart failure progression will not make it go away
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00105.2021. Online ahead of print.ABSTRACTA link between heart failure (HF) and low thyroid hormone (TH) function has been known for over a century. Nonetheless, there is a general belief that TH treatment of HF patients may not be worth the risk. This is largely based on two clinical trials where heart patients were treated with excessive doses of TH analogs, not actual THs. Further complicating the issue is the fact that normalization of THs in non-cardiac patients can often be challenging. This issue is not going away as noted by a steady increase in TH-...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: A Martin Gerdes Michael A Portman Giorgio Iervasi Alessandro Pingitore David Kc Cooper Dimitri Novitzky Source Type: research

Role of arterial impairment in preeclampsia: should the paradigm shift?
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.01005.2020. Online ahead of print.ABSTRACTPreeclampsia is a worldwide pregnancy complication with serious short and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Maria M Pereira Juan Torrado Claudio Sosa Yanina Z ócalo Daniel Bia Source Type: research

Single Cell Transcriptomics Trajectory and Molecular Convergence of Clinically Relevant Mutations in Brugada Syndrome
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00061.2021. Online ahead of print.ABSTRACTBrugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence of clinically relevant mutations and to identify developmental cardiac cell types that are associated with BrS etiology, we collected 733 mutations represented by 16 sodium, calcium, potassium channels, regulatory and structural genes related to BrS. Among the clinically relevant mutations, 266 are unique singletons and 88 mutations are recurrent. We observed an over representation of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Richa Tambi Reem Abdel Hameid Asma Bankapur Nasna Nassir Ghausia Begum Alawi Alsheikh-Ali Mohammed Uddin Bakhrom K Berdiev Source Type: research

Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00869.2020. Online ahead of print.ABSTRACTHigh levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. P...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Paulina Bryl-G órecka Kreema James Kristina Torngren Inger Haraldsson Li-Ming Gan Sara Svedlund Bj örn Olde Thomas Laurell Elmir Omerovic David Erlinge Source Type: research

No Evidence of Racial Disparities in Blood Pressure Salt Sensitivity When Potassium Intake Exceeds Levels Recommended in the US Dietary Guidelines
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00980.2020. Online ahead of print.ABSTRACTOn average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/d, black adults do not appear more sensitive than white adults to BP effects of short-term...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Theodore W Kurtz Stephen E DiCarlo Michal Pravenec R Curtis Morris Source Type: research

Ignoring a basic pathophysiological mechanism of heart failure progression will not make it go away
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00105.2021. Online ahead of print.ABSTRACTA link between heart failure (HF) and low thyroid hormone (TH) function has been known for over a century. Nonetheless, there is a general belief that TH treatment of HF patients may not be worth the risk. This is largely based on two clinical trials where heart patients were treated with excessive doses of TH analogs, not actual THs. Further complicating the issue is the fact that normalization of THs in non-cardiac patients can often be challenging. This issue is not going away as noted by a steady increase in TH-...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: A Martin Gerdes Michael A Portman Giorgio Iervasi Alessandro Pingitore David Kc Cooper Dimitri Novitzky Source Type: research

Role of arterial impairment in preeclampsia: should the paradigm shift?
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.01005.2020. Online ahead of print.ABSTRACTPreeclampsia is a worldwide pregnancy complication with serious short and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Maria M Pereira Juan Torrado Claudio Sosa Yanina Z ócalo Daniel Bia Source Type: research

Single Cell Transcriptomics Trajectory and Molecular Convergence of Clinically Relevant Mutations in Brugada Syndrome
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00061.2021. Online ahead of print.ABSTRACTBrugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence of clinically relevant mutations and to identify developmental cardiac cell types that are associated with BrS etiology, we collected 733 mutations represented by 16 sodium, calcium, potassium channels, regulatory and structural genes related to BrS. Among the clinically relevant mutations, 266 are unique singletons and 88 mutations are recurrent. We observed an over representation of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Richa Tambi Reem Abdel Hameid Asma Bankapur Nasna Nassir Ghausia Begum Alawi Alsheikh-Ali Mohammed Uddin Bakhrom K Berdiev Source Type: research

Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00869.2020. Online ahead of print.ABSTRACTHigh levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of cardiovascular patients. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. P...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Paulina Bryl-G órecka Kreema James Kristina Torngren Inger Haraldsson Li-Ming Gan Sara Svedlund Bj örn Olde Thomas Laurell Elmir Omerovic David Erlinge Source Type: research

No Evidence of Racial Disparities in Blood Pressure Salt Sensitivity When Potassium Intake Exceeds Levels Recommended in the US Dietary Guidelines
Am J Physiol Heart Circ Physiol. 2021 Apr 2. doi: 10.1152/ajpheart.00980.2020. Online ahead of print.ABSTRACTOn average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/d, black adults do not appear more sensitive than white adults to BP effects of short-term...
Source: American Journal of Physiology. Heart and Circulatory Physiology - April 2, 2021 Category: Physiology Authors: Theodore W Kurtz Stephen E DiCarlo Michal Pravenec R Curtis Morris Source Type: research

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00023.2021. Online ahead of print.ABSTRACTAfrican American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: DeWayne P Williams Julian F Thayer James D Halbert Xiaoling Wang Gaston Kapuku Source Type: research

Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Julian C Dunkley Camila I Irion Keyvan Yousefi Serene A Shehadeh Guerline Lambert Krista John-Williams Keith A Webster Jeffrey J Goldberger Lina A Shehadeh Source Type: research

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hU...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Wei Luo Yanshan Gong Fan Qiu Yi Yuan Wenwen Jia Zhongmin Liu Ling Gao Source Type: research

Cardiac nicotinic receptors show β-subunit dependent compensatory changes
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the rela...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research

Exercise in Hypertrophic Cardiomyopathy: Restrict or Rethink??
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00850.2020. Online ahead of print.ABSTRACTThe detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM) are not well understood. In athletes and non-athletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g. promoting hypertrophy, fibrosis), and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restrictio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Adaya Weissler Snir Kim A Connelly Jack M Goodman David Dorian Paul Dorian Source Type: research

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00036.2021. Online ahead of print.ABSTRACTHeart Failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of HF patients respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-gua...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Mark E Pepin Chae-Myeong Ha Luke A Potter Sayan Bakshi Joseph P Barchue Ayman Haj Asaad Steven M Pogwizd Salpy V Pamboukian Bertha A Hidalgo Selwyn M Vickers Adam R Wende Source Type: research

Regenerative Crosstalk between Cardiac Cells and Macrophages
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00056.2021. Online ahead of print.ABSTRACTAside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant crosstalk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Alexander J Whitehead Adam J Engler Source Type: research

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00023.2021. Online ahead of print.ABSTRACTAfrican American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: DeWayne P Williams Julian F Thayer James D Halbert Xiaoling Wang Gaston Kapuku Source Type: research

Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Julian C Dunkley Camila I Irion Keyvan Yousefi Serene A Shehadeh Guerline Lambert Krista John-Williams Keith A Webster Jeffrey J Goldberger Lina A Shehadeh Source Type: research

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hU...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Wei Luo Yanshan Gong Fan Qiu Yi Yuan Wenwen Jia Zhongmin Liu Ling Gao Source Type: research

Cardiac nicotinic receptors show β-subunit dependent compensatory changes
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the rela...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research

Exercise in Hypertrophic Cardiomyopathy: Restrict or Rethink??
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00850.2020. Online ahead of print.ABSTRACTThe detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM) are not well understood. In athletes and non-athletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g. promoting hypertrophy, fibrosis), and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restrictio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Adaya Weissler Snir Kim A Connelly Jack M Goodman David Dorian Paul Dorian Source Type: research

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00036.2021. Online ahead of print.ABSTRACTHeart Failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of HF patients respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-gua...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Mark E Pepin Chae-Myeong Ha Luke A Potter Sayan Bakshi Joseph P Barchue Ayman Haj Asaad Steven M Pogwizd Salpy V Pamboukian Bertha A Hidalgo Selwyn M Vickers Adam R Wende Source Type: research

Regenerative Crosstalk between Cardiac Cells and Macrophages
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00056.2021. Online ahead of print.ABSTRACTAside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant crosstalk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Alexander J Whitehead Adam J Engler Source Type: research

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00023.2021. Online ahead of print.ABSTRACTAfrican American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: DeWayne P Williams Julian F Thayer James D Halbert Xiaoling Wang Gaston Kapuku Source Type: research

Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Julian C Dunkley Camila I Irion Keyvan Yousefi Serene A Shehadeh Guerline Lambert Krista John-Williams Keith A Webster Jeffrey J Goldberger Lina A Shehadeh Source Type: research

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hU...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Wei Luo Yanshan Gong Fan Qiu Yi Yuan Wenwen Jia Zhongmin Liu Ling Gao Source Type: research

Cardiac nicotinic receptors show β-subunit dependent compensatory changes
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the rela...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research

Exercise in Hypertrophic Cardiomyopathy: Restrict or Rethink??
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00850.2020. Online ahead of print.ABSTRACTThe detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM) are not well understood. In athletes and non-athletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g. promoting hypertrophy, fibrosis), and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restrictio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Adaya Weissler Snir Kim A Connelly Jack M Goodman David Dorian Paul Dorian Source Type: research

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00036.2021. Online ahead of print.ABSTRACTHeart Failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of HF patients respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-gua...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Mark E Pepin Chae-Myeong Ha Luke A Potter Sayan Bakshi Joseph P Barchue Ayman Haj Asaad Steven M Pogwizd Salpy V Pamboukian Bertha A Hidalgo Selwyn M Vickers Adam R Wende Source Type: research

Regenerative Crosstalk between Cardiac Cells and Macrophages
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00056.2021. Online ahead of print.ABSTRACTAside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant crosstalk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Alexander J Whitehead Adam J Engler Source Type: research

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00023.2021. Online ahead of print.ABSTRACTAfrican American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: DeWayne P Williams Julian F Thayer James D Halbert Xiaoling Wang Gaston Kapuku Source Type: research

Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Julian C Dunkley Camila I Irion Keyvan Yousefi Serene A Shehadeh Guerline Lambert Krista John-Williams Keith A Webster Jeffrey J Goldberger Lina A Shehadeh Source Type: research

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hU...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Wei Luo Yanshan Gong Fan Qiu Yi Yuan Wenwen Jia Zhongmin Liu Ling Gao Source Type: research

Cardiac nicotinic receptors show β-subunit dependent compensatory changes
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the rela...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research

Exercise in Hypertrophic Cardiomyopathy: Restrict or Rethink??
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00850.2020. Online ahead of print.ABSTRACTThe detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM) are not well understood. In athletes and non-athletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g. promoting hypertrophy, fibrosis), and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restrictio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Adaya Weissler Snir Kim A Connelly Jack M Goodman David Dorian Paul Dorian Source Type: research

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00036.2021. Online ahead of print.ABSTRACTHeart Failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of HF patients respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-gua...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Mark E Pepin Chae-Myeong Ha Luke A Potter Sayan Bakshi Joseph P Barchue Ayman Haj Asaad Steven M Pogwizd Salpy V Pamboukian Bertha A Hidalgo Selwyn M Vickers Adam R Wende Source Type: research

Regenerative Crosstalk between Cardiac Cells and Macrophages
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00056.2021. Online ahead of print.ABSTRACTAside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant crosstalk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Alexander J Whitehead Adam J Engler Source Type: research

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00023.2021. Online ahead of print.ABSTRACTAfrican American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: DeWayne P Williams Julian F Thayer James D Halbert Xiaoling Wang Gaston Kapuku Source Type: research

Carvedilol and Exercise Combination Therapy Improves Systolic but not Diastolic Function and Reduces Plasma Osteopontin in Col4a3-/- Mice
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00535.2020. Online ahead of print.ABSTRACTThere are currently no FDA-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the Phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n=29), carvedilol (n=11), voluntary exercise (n=9), combination carvedilol and exercise (n=8). Cardiac function was assessed...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Julian C Dunkley Camila I Irion Keyvan Yousefi Serene A Shehadeh Guerline Lambert Krista John-Williams Keith A Webster Jeffrey J Goldberger Lina A Shehadeh Source Type: research

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair
In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hU...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Wei Luo Yanshan Gong Fan Qiu Yi Yuan Wenwen Jia Zhongmin Liu Ling Gao Source Type: research

Cardiac nicotinic receptors show β-subunit dependent compensatory changes
Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the rela...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research