Remote ischemic preconditioning reduces myocardial ischemia –reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway
This study aimed to determine whether ghrelin serves as one of the humoral factors in RIPC. RIPC group rats were subjected to three cycles of ischemia and reperfusion for 5 min in two limbs before left anterior descending (LAD) coronary artery ligation. Un acylated ghrelin (UAG) group rats were given 0.5 mcg/kg UAG intravenously 30 min before LAD ligation. Plasma levels of UAG in all groups were measured before and after RIPC procedures and UAG administration. Additionally, JAK2/STAT3 pathway inhibitor (AG490) was injected in RIPC and UAG groups to i nvestigate abolishment of the cardioprotection of RIPC and UAG....
Source: Basic Research in Cardiology - June 30, 2020 Category: Cardiology Source Type: research

Nuclear localization of a novel calpain-2 mediated junctophilin-2 C-terminal cleavage peptide promotes cardiomyocyte remodeling
In this study, we used Labcas to bioin formatically predict putative calpain cleavage sites on JPH2. We identified a cleavage site that produces a novel C-terminal JPH2 peptide (JPH2-CTP) using several domain-specific antibodies. Western blotting revealed elevated JPH2-CTP levels in hearts of patients and mice with HF, corresponding to i ncreased levels of calpain-2. Moreover, immunocytochemistry demonstrated nuclear localization of JPH2-CTP within ventricular myocytes isolated from a murine model of pressure overload-induced HF as well as rat ventricular myocytes treated with isoproterenol. Nuclear localization of JPH2-CT...
Source: Basic Research in Cardiology - June 26, 2020 Category: Cardiology Source Type: research

Secreted frizzled-related protein 2, a novel mechanism to induce myocardial ischemic protection through angiogenesis
AbstractOur hypothesis is that Secreted Frizzled-Related Protein 2 (sFPR2) is an important mechanism mediating ischemic cardioprotection, since it is the most upregulated gene in the third window of ischemic preconditioning. One week after permanent coronary artery occlusion (CAO), sFRP2 TG mice exhibited a 49% higher LV ejection fraction and a 36% reduction in infarct size,p 
Source: Basic Research in Cardiology - June 26, 2020 Category: Cardiology Source Type: research

Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis
AbstractAtherosclerosis is crucially fueled by inflammatory pathways including pattern recognition receptor (PRR)-related signaling of the innate immune system. Currently, the impact of the cytoplasmic PRRs nucleotide-binding oligomerization domain-containing protein (NOD) 1 and 2 is incompletely characterized. We, therefore, generatedNod1/Nod2 double knockout mice on a low-density lipoprotein receptor (Ldlr)-deficient background (=  Ldlr−/−Nod1/2−/−) which were subsequently analyzed regarding experimental atherosclerosis, lipid metabolism, insulin resistance and gut microbiota composition. C...
Source: Basic Research in Cardiology - June 25, 2020 Category: Cardiology Source Type: research

The inotropic agent digitoxin strengthens desmosomal adhesion in cardiac myocytes in an ERK1/2-dependent manner
AbstractDesmosomal proteins are components of the intercalated disc and mediate cardiac myocyte adhesion. Enhancement of cardiac myocyte cohesion, referred to as “positive adhesiotropy”, was demonstrated to be a function of sympathetic signaling and to be relevant for a sufficient inotropic response. We used the inotropic agent digitoxin to investigate the link between inotropy and adhesiotropy. In contrast to wild-type hearts, digitoxin failed to enhanc e pulse pressure in perfused mice hearts lacking the desmosomal protein plakoglobin which was paralleled with abrogation of plaque thickening indicating that p...
Source: Basic Research in Cardiology - June 17, 2020 Category: Cardiology Source Type: research

Deletion of newly described pro-survival molecule Pellino-1 increases oxidative stress, downregulates cIAP2/NF- κB cell survival pathway, reduces angiogenic response, and thereby aggravates tissue function in mouse ischemic models
ConclusionThese results suggest new insights into the protective role of Peli1 on ischemic tissues and its influence on survival signaling. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - June 14, 2020 Category: Cardiology Source Type: research

Anaemia is associated with severe RBC dysfunction and a reduced circulating NO pool: vascular and cardiac eNOS are crucial for the adaptation to anaemia
AbstractAnaemia is frequently present in patients with acute myocardial infarction (AMI) and contributes to an adverse prognosis. We hypothesised that, besides reduced oxygen carrying capacity, anaemia is associated with (1) red blood cell (RBC) dysfunction and a reduced circulating nitric oxide (NO) pool, (2) compensatory enhancement of vascular and cardiac endothelial nitric oxide synthase (eNOS) activity, and (3) contribution of both, RBC dysfunction and reduced circulatory NO pool to left ventricular (LV) dysfunction and fatal outcome in AMI. In mouse models of subacute and chronic anaemia from repeated mild blood loss...
Source: Basic Research in Cardiology - June 12, 2020 Category: Cardiology Source Type: research

Interplay of the red blood cell and vascular endothelial nitric oxide synthase system to combat cardiac complications of anemia
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - June 12, 2020 Category: Cardiology Source Type: research

Inflammation shapes pathogenesis of murine arrhythmogenic cardiomyopathy
AbstractArrhythmogenic cardiomyopathy (AC) is an incurable genetic disease, whose pathogenesis is poorly understood. AC is characterized by arrhythmia, fibrosis, and cardiodilation that may lead to sudden cardiac death or heart failure. To elucidate AC pathogenesis and to design possible treatment strategies of AC, multiple murine models have been established. Among them, mice carrying desmoglein 2 mutations are particularly valuable given the identification of desmoglein 2 mutations in human AC and the detection of desmoglein 2 auto-antibodies in AC patients. Using two mouse strains producing either a mutant desmoglein 2 ...
Source: Basic Research in Cardiology - June 12, 2020 Category: Cardiology Source Type: research

Vascular autophagy in health and disease
AbstractHomeostasis is maintained within organisms through the physiological recycling process of autophagy, a catabolic process that is intricately involved in the mobilization of nutrients during starvation, recycling of cellular cargo, as well as initiation of cellular death pathways. Specific to the cardiovascular system, autophagy responds to both chemical (e.g. free radicals) and mechanical stressors (e.g. shear stress). It is imperative to note that autophagy is not a static process, and measurement of autophagic flux provides a more comprehensive investigation into the role of autophagy. The overarching themes emer...
Source: Basic Research in Cardiology - June 6, 2020 Category: Cardiology Source Type: research

Intravenously delivered mesenchymal stem cells prevent microvascular obstruction formation after myocardial ischemia/reperfusion injury
AbstractMicrovascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction (AMI). The inflammatory response induced by ischemia and reperfusion (I/R) injury is considered one of the main mechanisms of MVO. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers an immunomodulatory effect in cardiac disease. The present study aimed to investigate whether immediate intravenous delivery of MSCs could be used as a potential therapeutic method to attenuate MVO formation. A cardiac ca...
Source: Basic Research in Cardiology - May 25, 2020 Category: Cardiology Source Type: research

Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities
AbstractHeart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous disease for which our pathophysiological understanding is still limited and specific prevention and treatment strategies are lacking. HFpEF is characterised by diastolic dysfunction and cardiac remodelling (fibrosis, inflammation, and hypertrophy). Recently, microvascular dysfunction and chronic low-grade inflammation have been proposed to participate in HFpEF development. Furthermore, several recent studies demonstrated the occurrence of generalized lymphatic dysfunction in experimental models of risk factors for HFpEF, including obe...
Source: Basic Research in Cardiology - May 25, 2020 Category: Cardiology Source Type: research

Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS
In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca2+ leak, via altered SR-mitochondrial Ca2+ transfer and elevated mito-ROS emission. Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and catecholaminergic polymorphic ventricular tachycardia (CPVT) mice, respectively, resulted in increased ROS emission under β-adrenergic stimulation. Expression of mitochondrial Ca2+ probe mtRCamp1h revealed diminished net mitochondrial [Ca2+] with enha...
Source: Basic Research in Cardiology - May 22, 2020 Category: Cardiology Source Type: research

Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells
AbstractHuman-induced pluripotent stem cells (h-iPSCs) are a unique in vitro model for cardiovascular research. To realize the potential applications of h-iPSCs-derived cardiomyocytes (CMs) for drug testing or regenerative medicine and disease modeling, characterization of the metabolic features is critical. Here, we show the transcriptional profile during stages of cardiomyogenesis of h-iPSCs-derived CMs. CM differentiation was not only characterized by the expression of mature structural components (MLC2v, MYH7) but also accompanied by a significant increase in mature metabolic gene expression and activity. Our data reve...
Source: Basic Research in Cardiology - May 18, 2020 Category: Cardiology Source Type: research

Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series
AbstractThere are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukoc...
Source: Basic Research in Cardiology - May 12, 2020 Category: Cardiology Source Type: research

A future for remote ischaemic conditioning in high-risk patients
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 25, 2020 Category: Cardiology Source Type: research

The endocannabinoid anandamide has an anti-inflammatory effect on CCL2 expression in vascular smooth muscle cells
This study therefore est ablishes a novel anti-inflammatory mechanism for the endogenous endocannabinoid AEA in vascular smooth muscle cells. Furthermore, this work provides a link between endogenous endocannabinoid signaling and epigenetic regulation. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 22, 2020 Category: Cardiology Source Type: research

Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging
AbstractNonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodal...
Source: Basic Research in Cardiology - April 14, 2020 Category: Cardiology Source Type: research

Perspective: cardiovascular disease and the Covid-19 pandemic
AbstractWe summarize the cardiovascular risks associated with Covid-19 pandemic, discussing the risks for both infected and non-infected patients. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 10, 2020 Category: Cardiology Source Type: research

COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm?
In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 9, 2020 Category: Cardiology Source Type: research

Matrix metalloproteinase-7 in platelet-activated macrophages accounts for cardiac remodeling in uremic mice
AbstractHeart failure is the leading cause of mortality in patients with end-stage renal disease, and progressive cardiac remodeling is the key pathological basis of heart failure. However, the mechanism by which uremia-induced cardiac remodeling occurs is not well understood. Here, we showed that platelets were significantly activated in 5/6 nephrectomy-operated mice, and cardiac remodeling in the uremic mice was significantly improved when platelets were effectively depleted. A cardiac fibrosis-related gene expression profile revealed thatMmp7, encoding matrix metalloproteinase-7 (MMP-7), exhibited the greatest degree of...
Source: Basic Research in Cardiology - April 9, 2020 Category: Cardiology Source Type: research

CARD9 promotes autophagy in cardiomyocytes in myocardial ischemia/reperfusion injury via interacting with Rubicon directly
AbstractAutophagy in cardiomyocyte is involved in myocardial ischemia/reperfusion (M-I/R) injury. Caspase recruitment domain-containing protein 9 (CARD9) plays a critical role in cardiovascular diseases (CVDs) such as hypertension and cardiac fibrosis. However, its role in autophagy following M-I/R injury is yet to be fully elucidated. Here, we found that CARD9 expression increased in M-I/R mouse hearts, and in H9c2 or neonatal rat ventricular myocytes (NRVMs) in response to hypoxia/reoxygenation (H/R) or H2O2. CARD9−/− mice exhibited a significant cardiac dysfunction following M-I/R injury (30  min of lef...
Source: Basic Research in Cardiology - April 4, 2020 Category: Cardiology Source Type: research

Exercise improves cardiac function and glucose metabolism in mice with experimental myocardial infarction through inhibiting HDAC4 and upregulating GLUT1 expression
In conclusion, exercise improves cardiac function and glucose metabolism in HF mice through inhibiting HDAC4 and upregulating GLUT1 expression. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 31, 2020 Category: Cardiology Source Type: research

CRISPLD1: a novel conserved target in the transition to human heart failure
AbstractHeart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular proces...
Source: Basic Research in Cardiology - March 7, 2020 Category: Cardiology Source Type: research

Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential
AbstractMesenchymal stromal cells (MSCs) exhibit antiapoptotic and proangiogenic functions in models of myocardial infarction which may be mediated by secreted small extracellular vesicles (sEVs). However, MSCs have frequently been harvested from aged or diseased patients, while the isolated sEVs often contain high levels of impurities. Here, we studied the cardioprotective and proangiogenic activities of size-exclusion chromatography-purified sEVs secreted from human foetal amniotic fluid stem cells (SS-hAFSCs), possessing superior functional potential to that of adult MSCs. We demonstrated for the first time that highly ...
Source: Basic Research in Cardiology - March 7, 2020 Category: Cardiology Source Type: research

Correction to: DNA ‑PKcs promotes cardiac ischemia reperfusion injury through mitigating BI‑1‑governed mitochondrial homeostasis
Since the publication of the article, the authors found a small problem with Fig.  7e. Unfortunately, Fig. 7e did not contain the correct images. The correct images are shown below and do not change the conclusions. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - March 6, 2020 Category: Cardiology Source Type: research

Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction
AbstractIntramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia –reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent ...
Source: Basic Research in Cardiology - March 5, 2020 Category: Cardiology Source Type: research

Mitochondrial noncoding RNA-regulatory network in cardiovascular disease
AbstractMitochondrial function and integrity are vital for the maintenance of cellular homeostasis, particularly in high-energy demanding cells. Cardiomyocytes have a large number of mitochondria, which provide a continuous and bulk supply of the ATP necessary for cardiac mechanical function. More than 90% of the ATP consumed by the heart is derived from the mitochondrial oxidative metabolism. Decreased energy supply as the main consequence of mitochondrial dysfunction is closely linked to cardiovascular disease (CVD). The discovery of noncoding RNA (ncRNAs) in the mitochondrial compartment has changed the traditional view...
Source: Basic Research in Cardiology - March 5, 2020 Category: Cardiology Source Type: research

M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment
In this study, we investigated the role of M1-like macrophage-derived exosomes in a MI microenvironment. We found that the proinflammatory M1-like-type macrophages released an extensive array of proinflammatory exosomes (M1-Exos) after MI. M1-Exos exerted an anti-angiogenic effect and accelerated MI injury. They also exhibited highly expressed proinflammatory miRNAs, such as miR-155. miR-155 was transferred to endothelial cells (ECs), leading to the inhibition of angiogenesis and cardiac dysfunction by downregulating its novel target genes, including Rac family small GTPase 1 (RAC1), p21 (RAC1)-activated kinase 2 (PAK2), S...
Source: Basic Research in Cardiology - February 28, 2020 Category: Cardiology Source Type: research

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease
In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe en ough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - February 25, 2020 Category: Cardiology Source Type: research

Inhibition of Na V 1.8 prevents atrial arrhythmogenesis in human and mice
This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects ...
Source: Basic Research in Cardiology - February 20, 2020 Category: Cardiology Source Type: research

Triad3A attenuates pathological cardiac hypertrophy involving the augmentation of ubiquitination-mediated degradation of TLR4 and TLR9
AbstractActivation of TLRs mediated the NF- κB signaling pathway plays an important pathophysiological role in cardiac hypertrophy. Triad3A, a ubiquitin E3 ligase, has been reported to negatively regulate NF-κB activation pathway via promoting ubiquitination and degradation of TLR4 and TLR9 in innate immune cells. The role of Triad3A in car diac hypertrophic development remains unknown. The present study investigated whether there is a link between Triad3A and TLR4 and TLR9 in pressure overload induced cardiac hypertrophy. We observed that Triad3A levels were markedly reduced following transverse aortic constri...
Source: Basic Research in Cardiology - February 1, 2020 Category: Cardiology Source Type: research

Murine sca1/flk1-positive cells are not endothelial progenitor cells, but B2 lymphocytes
AbstractCirculating sca1+/flk1+ cells are hypothesized to be endothelial progenitor cells (EPCs) in mice that contribute to atheroprotection by replacing dysfunctional endothelial cells. Decreased numbers of circulating sca1+/flk1+ cells correlate with increased atherosclerotic lesions and impaired reendothelialization upon electric injury of the common carotid artery. However, legitimate doubts remain about the identity of the putative EPCs and their contribution to endothelial restoration. Hence, our study aimed to establish a phenotype for sca1+/flk1+ cells to gain a better understanding of their role in atherosclerotic...
Source: Basic Research in Cardiology - January 24, 2020 Category: Cardiology Source Type: research

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction
ConclusionFHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - January 24, 2020 Category: Cardiology Source Type: research

Selective intrarenal delivery of mesenchymal stem cell-derived extracellular vesicles attenuates myocardial injury in experimental metabolic renovascular disease
AbstractExtracellular vesicles (EVs) deliver genes and proteins to recipient cells, and mediate paracrine actions of their parent cells. Intrarenal delivery of mesenchymal stem cell (MSC)-derived EVs preserves stenotic-kidney function and reduces release of pro-inflammatory cytokines in a swine model of coexisting metabolic syndrome (MetS) and renal artery stenosis (RAS). We hypothesized that this approach is also capable of blunting cardiac injury and dysfunction. Five groups of pigs were studied after 16  weeks of diet-induced MetS and RAS (MetS + RAS), MetS and MetS + RAS treated 4 ...
Source: Basic Research in Cardiology - January 14, 2020 Category: Cardiology Source Type: research

Renal denervation restrains the inflammatory response in myocardial ischemia –reperfusion injury
AbstractMyocardial ischemia –reperfusion (I/R) injury leads to intensive sympathetic nervous system (SNS) activation and inflammatory reactions. Whether renal sympathetic denervation (RDN) could be a new therapeutic strategy to modulate I/R inflammation and reduce infarct size after myocardial I/R injury needs to be explored . First, we investigated the correlation between plasma norepinephrine concentrations and circulating myeloid cell numbers in patients with acute myocardial infarction. And then, C57BL/6 mice underwent a"two-hit" operation, with 10% phenol applied to bilateral renal nerves to abrogate s...
Source: Basic Research in Cardiology - January 13, 2020 Category: Cardiology Source Type: research

TRPV4 deletion protects heart from myocardial infarction-induced adverse remodeling via modulation of cardiac fibroblast differentiation
AbstractCardiac fibrosis caused by adverse cardiac remodeling following myocardial infarction can eventually lead to heart failure. Although the role of soluble factors such as TGF- β is well studied in cardiac fibrosis following myocardial injury, the physiological role of mechanotransduction is not fully understood. Here, we investigated the molecular mechanism and functional role of TRPV4 mechanotransduction in cardiac fibrosis. TRPV4KO mice, 8 weeks following myocardial i nfarction (MI), exhibited preserved cardiac function compared to WT mice. Histological analysis demonstrated reduced cardiac fibrosis in TR...
Source: Basic Research in Cardiology - January 10, 2020 Category: Cardiology Source Type: research

Overexpression of mitochondrial creatine kinase preserves cardiac energetics without ameliorating murine chronic heart failure
In conclusion, overexpression of Mt-CK activity prevented the changes in cardiac energetics that are considered hallmarks of a failing heart. This had a positive effect on early survival but was not associated with improved LV remodelling or function during the development of chronic heart failure. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - January 10, 2020 Category: Cardiology Source Type: research

Tryptophane –kynurenine pathway in the remote ischemic conditioning mechanism
AbstractThe actual protective mechanisms underlying cardioprotection with remote ischemic conditioning (RIC) remain unclear. Recent data suggest that RIC induces kynurenine (KYN) and kynurenic acid synthesis, two metabolites derived from tryptophan (TRP), yet a causal relation between TRP pathway and RIC remains to be established. We sought to study the impact of RIC on the levels of TRP and its main metabolites within tissues, and to assess whether blocking kynurenine (KYN) synthesis from TRP would inhibit RIC-induced cardioprotection. In rats exposed to 40-min coronary occlusion and 2-h reperfusion, infarct size was sign...
Source: Basic Research in Cardiology - January 10, 2020 Category: Cardiology Source Type: research

DNA-PKcs promotes cardiac ischemia reperfusion injury through mitigating BI-1-governed mitochondrial homeostasis
This study was designed to examine the role of DNA-PKcs in cardiac ischemia reperfusion (IR) injury and mitochondrial damage. Cardiomyocyte-specific DNA-PKcs knockout (DNA-PKcsCKO) mice were subjected to IR prior to assessment of myocardial function and mitochondrial apoptosis. Our data revealed that IR challenge, hypoxia-reoxygenation (HR) or H2O2-activated DNA-PKcs through post-transcriptional phosphorylation in murine hearts or cardiomyocytes. Mice deficient in DNA-PKcs in cardiomyocytes were protected against cardiomyocyte death, infarct area expansion and cardiac dysfunction. DNA-PKcs ablation countered IR- or HR-indu...
Source: Basic Research in Cardiology - January 9, 2020 Category: Cardiology Source Type: research

Thrombin receptor PAR4 drives canonical NLRP3 inflammasome signaling in the heart
In conclusion, PAR4 drives caspase-1-dependent IL-1β production through the canonical NLRP3 inflammasome pathway in the diabetic heart, providing mechanistic insights into diabetes-associated cardiac thromboin flammation. The emerging PAR4-selective antagonists may provide a feasible approach to prevent cardiac inflammation in patients with diabetes. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - January 7, 2020 Category: Cardiology Source Type: research

Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis
AbstractVentricular arrhythmia is the most common cause of sudden cardiac death in patients with myocardial infarction (MI). Fibroblast growth factor 21 (FGF21) has been shown to play an important role in cardiovascular and metabolic diseases. However, the effects of FGF21 on ventricular arrhythmias following MI have not been addressed yet. The present study was conducted to investigate the pharmacological action of FGF21 on ventricular arrhythmias after MI. Adult male mice were administrated with or without recombinant human basic FGF21 (rhbFGF21), and the susceptibility to arrhythmias was assessed by programmed electrica...
Source: Basic Research in Cardiology - January 4, 2020 Category: Cardiology Source Type: research

Distinct origins and functions of cardiac orthotopic macrophages
AbstractMacrophages are one cell type in the innate immune system. Recent studies involving macrophages have overturned the conventional concept that circulating bone marrow-derived blood mononuclear cells in the adult body continuously replace macrophages residing in the tissues. Investigations using refined technologies have suggested that embryonic hematopoiesis can result in the differentiation into macrophage subgroups in some tissues. In adulthood, these macrophages are self-sustaining via in situ proliferation, with little contribution of circulating bone marrow-derived blood mononuclear cells. Macrophages are integ...
Source: Basic Research in Cardiology - January 2, 2020 Category: Cardiology Source Type: research

Cell shape determines gene expression: cardiomyocyte morphotypic transcriptomes
AbstractCardiomyocytes undergo considerable changes in cell shape. These can be due to hemodynamic constraints, including changes in preload and afterload conditions, or to mutations in genes important for cardiac function. These changes instigate significant changes in cellular architecture and lead to the addition of sarcomeres, at the same time or at a later stage. However, it is currently unknown whether changes in cell shape on their own affect gene expression and the aim of this study was to fill that gap in our knowledge. We developed a single-cell morphotyping strategy, followed by single-cell RNA sequencing, to de...
Source: Basic Research in Cardiology - December 23, 2019 Category: Cardiology Source Type: research

Heart non-specific effector CD4 + T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis
In this study, we provided a proof-of-concept that heart non-specificTeff cells could effectively contribute to myocarditis and protect the heart from the dilated cardiomyopathy outcome. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - December 20, 2019 Category: Cardiology Source Type: research

Importance of infarct size versus other variables for clinical outcomes after PPCI in STEMI patients
AbstractDespite promising experimental studies and encouraging proof-of-concept clinical trials, interventions aimed at limiting infarct size have failed to improve clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Our objective was to examine whether variables (cardiovascular risk factors, comorbidities, post-procedural variables, cotreatments) might be associated with clinical outcomes in STEMI patients independently from infarct size reduction. The present study was based on a post hoc analysis of the CIRCUS trial database (Clinicaltrials.gov NCT01502774) that assessed the clinical benefit &...
Source: Basic Research in Cardiology - December 12, 2019 Category: Cardiology Source Type: research

The changing face after acute myocardial infarction
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - December 12, 2019 Category: Cardiology Source Type: research

Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection
This study used H9C2 cells in vitro and a rat model of cardiac ischemia reperfusion (I/R) injury. We silenced Egr-1 with DNAzyme (ED5) in vitro and in vivo, before three cycles of RIPC consisting of alternating 5  min hypoxia and normoxia in cells or hind-limb ligation and release in the rat, followed by hypoxic challenge in vitro and I/R injury in vivo. Post-procedure, ED5 administration led to a significant increase in infarct size compared to controls (65.90 ± 2.38% vs. 41.00 ± 2.83%,p 
Source: Basic Research in Cardiology - December 10, 2019 Category: Cardiology Source Type: research

Molecular pathways involved in the cardioprotective effects of intravenous statin administration during ischemia
AbstractThe success of therapies targeting myocardial reperfusion injury is limited, while the cardioprotective impact of mitigating ischemia-related damage remains less explored. We have recently shown in a pig model that the intravenous administration of a modified atorvastatin preparation during ischemia attenuates the rise of cardiac ischemia injury biomarkers. In the following study, we sought to investigate the mechanisms behind these ischemia-related cardioprotective effects. Ischemia was induced by 90  min total coronary balloon occlusion in pigs fed a normocholesterolemic regime. Fifteen minutes after the ons...
Source: Basic Research in Cardiology - November 28, 2019 Category: Cardiology Source Type: research

Mitochondrial connexin 43 in sex-dependent myocardial responses and estrogen-mediated cardiac protection following acute ischemia/reperfusion injury
AbstractPreserving mitochondrial activity is crucial in rescuing cardiac function following acute myocardial ischemia/reperfusion (I/R). The sex difference in myocardial functional recovery has been observed after I/R. Given the key role of mitochondrial connexin43 (Cx43) in cardiac protection initiated by ischemic preconditioning, we aimed to determine the implication of mitochondrial Cx43 in sex-related myocardial responses and to  examine the effect of estrogen (17β-estradiol, E2) on Cx43, particularly mitochondrial Cx43-involved cardiac protection following I/R. Mouse primary cardiomyocytes and isolated mouse...
Source: Basic Research in Cardiology - November 18, 2019 Category: Cardiology Source Type: research