Blunting TRPML1 channels protects myocardial ischemia/reperfusion injury by restoring impaired cardiomyocyte autophagy
AbstractAccumulating evidence suggests that autophagy dysfunction plays a critical role in myocardial ischemia/reperfusion (I/R) injury. However, the underling mechanism of malfunctional autophagy in the cardiomyocytes subjected to I/R has not been well defined. As a result, there is no effective therapeutic option by targeting autophagy to prevent myocardial I/R injury. Here, we used both an in vitro and an in vivo I/R model to monitor autophagic flux in the cardiomyocytes, by exposing neonatal rat ventricular myocytes to hypoxia/reoxygenation and by subjecting mice to I/R, respectively. We observed that the autophagic fl...
Source: Basic Research in Cardiology - April 7, 2022 Category: Cardiology Source Type: research
Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs
AbstractInflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham,n = 5)....
Source: Basic Research in Cardiology - April 7, 2022 Category: Cardiology Source Type: research
Blunting TRPML1 channels protects myocardial ischemia/reperfusion injury by restoring impaired cardiomyocyte autophagy
AbstractAccumulating evidence suggests that autophagy dysfunction plays a critical role in myocardial ischemia/reperfusion (I/R) injury. However, the underling mechanism of malfunctional autophagy in the cardiomyocytes subjected to I/R has not been well defined. As a result, there is no effective therapeutic option by targeting autophagy to prevent myocardial I/R injury. Here, we used both an in vitro and an in vivo I/R model to monitor autophagic flux in the cardiomyocytes, by exposing neonatal rat ventricular myocytes to hypoxia/reoxygenation and by subjecting mice to I/R, respectively. We observed that the autophagic fl...
Source: Basic Research in Cardiology - April 7, 2022 Category: Cardiology Source Type: research
Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs
AbstractInflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham,n = 5)....
Source: Basic Research in Cardiology - April 7, 2022 Category: Cardiology Source Type: research
Nuclear Tkt promotes ischemic heart failure via the cleaved Parp1/Aif axis
AbstractTransketolase (Tkt), an enzyme in pentose phosphate pathway, has been reported to regulate genome instability and cell survival in cancers. Yet, the role of Tkt after myocardial ischemic injury remains to be elucidated. Label-free proteomics revealed dramatic elevation of Tkt in murine hearts after myocardial infarction (MI). Lentivirus-mediated Tkt knockdown ameliorated cardiomyocyte apoptosis and preserved the systolic function after myocardial ischemic injury. In contrast, Tkt overexpression led to the opposite effects. Inducible conditional cardiomyocyte Tkt-knockout mice were generated, and cardiomyocyte-expre...
Source: Basic Research in Cardiology - April 5, 2022 Category: Cardiology Source Type: research
Publisher Correction: Transcriptome-wide association study of coronary artery disease identifies novel susceptibility genes
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 5, 2022 Category: Cardiology Source Type: research
Alkaline nucleoplasm facilitates contractile gene expression in the mammalian heart
AbstractCardiac contractile strength is recognised as being highly pH-sensitive, but less is known about the influence of pH on cardiac gene expression, which may become relevant in response to changes in myocardial metabolism or vascularization during development or disease. We sought evidence for pH-responsive cardiac genes, and a physiological context for this form of transcriptional regulation. pHLIP, a peptide-based reporter of acidity, revealed a non-uniform pH landscape in early-postnatal myocardium, dissipating in later life. pH-responsive differentially expressed genes (pH-DEGs) were identified by transcriptomics ...
Source: Basic Research in Cardiology - March 31, 2022 Category: Cardiology Source Type: research
P2Y12-dependent activation of hematopoietic stem and progenitor cells promotes emergency hematopoiesis after myocardial infarction
In this study, we describe the influence of adenosine diphosphate (ADP)-dependent P2Y12-mediated signaling on emergency hematopoiesis and cardiac remodeling after MI. Permanent coronary ligation was performed to induce MI in a murine model. BM activation, inflammatory cell composition and cardiac function were assessed using global and platelet-specific gene knockout and pharmacological inhibition models for P2Y12. Complementary in vitro studies allowed for investigation of ADP-dependent effects on LSK cells. We found that ADP acts as a danger signal for the hematopoietic BM and fosters emergency hematopoiesis by promoting...
Source: Basic Research in Cardiology - March 30, 2022 Category: Cardiology Source Type: research
Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses
AbstractHyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and β-adrenoceptors (α-, β-ARs). As the relative contribution of subtype α1-AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the β-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α1-AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates ...
Source: Basic Research in Cardiology - March 14, 2022 Category: Cardiology Source Type: research
Characterizing the transition from immune response to tissue repair after myocardial infarction by multiparametric imaging
AbstractPersistent inflammation following myocardial infarction (MI) precipitates adverse outcome including acute ventricular rupture and chronic heart failure. Molecular imaging allows longitudinal assessment of immune cell activity in the infarct territory and predicts severity of remodeling. We utilized a multiparametric imaging platform to assess the immune response and cardiac healing following MI in mice. Suppression of circulating macrophages prior to MI paradoxically resulted in higher total leukocyte content in the heart, demonstrated by increased CXC motif chemokine receptor 4 (CXCR4) positron emission tomography...
Source: Basic Research in Cardiology - March 11, 2022 Category: Cardiology Source Type: research
Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients
In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Ou r results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 8, 2022 Category: Cardiology Source Type: research
On the cellular origin of cardiosphere-derived cells (CDCs)
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 8, 2022 Category: Cardiology Source Type: research
Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 8, 2022 Category: Cardiology Source Type: research
Loss of NPPA-AS1 promotes heart regeneration by stabilizing SFPQ –NONO heteromer-induced DNA repair
AbstractThe role of long non-coding RNA (lncRNA) in endogenous cardiac regeneration remains largely elusive. The mammalian cardiomyocyte is capable of regeneration for a brief period after birth. This fact allows the exploration of the roles of critical lncRNAs in the regulation of cardiac regeneration. Through a cardiac regeneration model by apical resection (AR) of the left ventricle in neonatal mice, we identified an lncRNA named natriuretic peptide A antisense RNA 1 (NPPA-AS1), which negatively regulated cardiomyocyte proliferation. In neonates, NPPA-AS1 deletion did not affect heart development, but was sufficient to ...
Source: Basic Research in Cardiology - March 5, 2022 Category: Cardiology Source Type: research
Development and characterization of anti-fibrotic natural compound similars with improved effectivity
AbstractCardiac fibroblasts constitute the major cell type of the murine and human heart. Once activated, they contribute to an excessive deposition of extracellular matrix (ECM) leading to cardiac fibrosis and subsequently organ dysfunction. With the exception of the pulmonary drugs, nintedanib and pirfenidone, drugs specifically targeting anti-fibrotic pathways are scarce. We recently performed large library screenings of natural occurring compounds and identified first lead structures with anti-fibrotic properties in vitro and in vivo. In line, we now aimed to improve efficacy of these anti-fibrotic lead structures by c...
Source: Basic Research in Cardiology - March 2, 2022 Category: Cardiology Source Type: research
