RGS3L allows for an M2 muscarinic receptor-mediated RhoA-dependent inotropy in cardiomyocytes
AbstractThe role and outcome of the muscarinic M2 acetylcholine receptor (M2R) signaling in healthy and diseased cardiomyocytes is still a matter of debate. Here, we report that the long isoform of the regulator of G protein signaling 3 (RGS3L) functions as a switch in the muscarinic signaling, most likely of the M2R, in primary cardiomyocytes. High levels of RGS3L, as found in heart failure, redirect the Gi-mediated Rac1 activation into a Gi-mediated RhoA/ROCK activation. Functionally, this switch resulted in a reduced production of reactive oxygen species ( − 50%) in cardiomyocytes and an inotropic response (+ 18%)...
Source: Basic Research in Cardiology - March 1, 2022 Category: Cardiology Source Type: research
Correction to: Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice
(Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - February 28, 2022 Category: Cardiology Source Type: research
Transcriptome-wide association study of coronary artery disease identifies novel susceptibility genes
AbstractThe majority of risk loci identified by genome-wide association studies (GWAS) are in non-coding regions, hampering their functional interpretation. Instead, transcriptome-wide association studies (TWAS) identify gene-trait associations, which can be used to prioritize candidate genes in disease-relevant tissue(s). Here, we aimed to systematically identify susceptibility genes for coronary artery disease (CAD) by TWAS. We trained prediction models of nine CAD-relevant tissues using EpiXcan based on two genetics-of-gene-expression panels, the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET)...
Source: Basic Research in Cardiology - February 17, 2022 Category: Cardiology Source Type: research
Reverse re-modelling chronic heart failure by reinstating heart rate variability
AbstractHeart rate variability (HRV) is a crucial indicator of cardiovascular health. Low HRV is correlated with disease severity and mortality in heart failure. Heart rate increases and decreases with each breath in normal physiology termed respiratory sinus arrhythmia (RSA). RSA is highly evolutionarily conserved, most prominent in the young and athletic and is lost in cardiovascular disease. Despite this, current pacemakers either pace the heart in a metronomic fashion or sense activity in the sinus node. If RSA has been lost in cardiovascular disease current pacemakers cannot restore it. We hypothesized that restoratio...
Source: Basic Research in Cardiology - February 1, 2022 Category: Cardiology Source Type: research
Mitochondrial DNA integrity and function are critical for endothelium-dependent vasodilation in rats with metabolic syndrome
AbstractEndothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10–3 M) compared to Zucker Lean rats (ZLN, 9...
Source: Basic Research in Cardiology - January 17, 2022 Category: Cardiology Source Type: research
Mechanism of the switch from NO to H2O2 in endothelium-dependent vasodilation in diabetes
This study represents the first mouse model recapitulating the NO-to-H2O2 switch seen in CAD patients in diabetes. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - January 13, 2022 Category: Cardiology Source Type: research
Coronary blood flow in heart failure: cause, consequence and bystander
AbstractHeart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic h...
Source: Basic Research in Cardiology - January 13, 2022 Category: Cardiology Source Type: research
Mechanism of the switch from NO to H2O2 in endothelium-dependent vasodilation in diabetes
This study represents the first mouse model recapitulating the NO-to-H2O2 switch seen in CAD patients in diabetes. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - January 13, 2022 Category: Cardiology Source Type: research
Coronary blood flow in heart failure: cause, consequence and bystander
AbstractHeart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic h...
Source: Basic Research in Cardiology - January 13, 2022 Category: Cardiology Source Type: research
Increased protein S-nitrosylation in mitochondria: a key mechanism of exercise-induced cardioprotection
AbstractEndothelial nitric oxide synthase (eNOS) activation in the heart plays a key role in exercise-induced cardioprotection during ischemia –reperfusion, but the underlying mechanisms remain unknown. We hypothesized that the cardioprotective effect of exercise training could be explained by the re-localization of eNOS-dependent nitric oxide (NO)/S-nitrosylation signaling to mitochondria. By comparing exercised (5 days/week for 5 weeks) and sedentary Wistar rats, we found that exercise training increased eNOS level and activation by phosphorylation (at serine 1177) in mitochondria, but not in the cytosolic subfracti...
Source: Basic Research in Cardiology - December 23, 2021 Category: Cardiology Source Type: research
Protective effect of HINT2 on mitochondrial function via repressing MCU complex activation attenuates cardiac microvascular ischemia –reperfusion injury
In conclusion, the present report demonstrated that HINT2 overexpression inhibited MCU complex-mitochondrial calcium overload-mitochondrial fission and apoptosis pathway, and thereby attenuated cardiac microvascular ischemia –reperfusion injury. (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - December 16, 2021 Category: Cardiology Source Type: research
Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation
In this study, Increased glucose metabolism of cardiac macrophages was found in patients with AR. To find new therapeutic targets of immune metabolism regulation for AR, CD45+ immune cells extracted from murine isografts, allografts, and untransplanted donor hearts were explored by single-cell RNA sequencing. Total 20 immune cell subtypes were identified among 46,040 cells. The function of immune cells in AR were illustrated simultaneously. Cardiac resident macrophages were substantially replaced by monocytes and proinflammatory macrophages during AR. Monocytes/macrophages in AR allograft were more active in antigen presen...
Source: Basic Research in Cardiology - December 6, 2021 Category: Cardiology Source Type: research
