PubMed Journal Database | Journal of molecular and cellular cardiology RSS

08:07 EDT 24th May 2019 | BioPortfolio

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Showing PubMed Articles 1–25 of 295 from Journal of molecular and cellular cardiology

Transcript levels for extracellular matrix proteins are altered in MK5-deficient cardiac ventricular fibroblasts.

MK5 is a protein serine/threonine kinase activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. Although little is known of the physiological role of MK5 in the heart, both hypertrophic growth and the increase in collagen 1-α mRNA induced by increased afterload are attenuated in hearts of MK5 haploinsufficient (MK5) mice. MK5 transcripts are detected at high levels in the left ventricular myocardium; however, MK5 immunoreactivity is detected in adult cardiac fibroblasts, but not myocytes. The present ...

An overview of the molecular mechanisms underlying development and progression of bicuspid aortic valve disease.

Bicuspid aortic valve (BAV) is a common congenital heart malformation frequently associated with the development of aortic valve diseases and severe aortopathy, such as aortic dilatation, aneurysm and dissection. To date, different genetic loci have been identified in syndromic and not syndromic forms of BAV. Among these, genes involved in the regulation of extracellular matrix remodelling, epithelial to mesenchymal transition and nitric oxide metabolism appear to be the main contributors to BAV pathogenesi...

Correlational study on altered epicardial adipose tissue as a stratification risk factor for valve disease progression through IL-13 signaling.

Genetic and environmental factors all interact in the risk of progression of valvular dysfunctions. Previous studies reported a relation between valve diseases and epicardial adipose tissue (EAT) thickness. The aim of this study was to verify the possible relationship between the molecular pattern of EAT related to IL-13 fibrogenic cytokine expression and valve dysfunction.

Involvement of circulating inflammatory factors in prognosis and risk of cardiovascular disease.

Cardiovascular disease (CVD) is an inflammatory disease that different factors play a crucial role in the development of clinical outcome of this disease. Inflammation could have effects on initiation, progression, and clinical complications of CVD. Previous studies have indicated that delineating the underlying mechanisms of inflammatory factors involved in this disease should be considerably beneficial both as predictive markers and targets for advancement of appropriate therapeutic approaches in offsetti...

MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24.

microRNA-124(miR-124) has recently been reported to be elevated in cardiovascular disease. In this study, we aimed to investigate the exact role of miR-124 in cardiomyocytes and myocardial infarction, identifying the functional target and its regulatory mechanisms.

Inhibition of PI3Kinase-α is pro-arrhythmic and associated with enhanced late Na current, contractility, and Ca release in murine hearts.

Phosphoinositide 3-kinase α (PI3Kα) is a proto-oncogene with high activity in the heart. BYL719 (BYL) is a PI3Kα-selective small molecule inhibitor and a prospective drug for advanced solid tumors. We investigated whether acute pharmacological inhibition of PI3Kα has pro-arrhythmic effects.

The critical role of the zinc transporter Zip2 (SLC39A2) in ischemia/reperfusion injury in mouse hearts.

Although zinc homeostasis has been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury, the roles of zinc transporters that are critical for zinc homeostasis in I/R injury are poorly understood. The purpose of this study was to test if Zip2, an important zinc importer, plays a role in I/R injury in mouse hearts and explore the mechanism by which Zip2 expression is regulated. Zip2 expression was increased at reperfusion in in vivo mouse hearts, an effect that was abolished by ZnCl, in...

Electrophysiologic and molecular mechanisms of a frameshift NPPA mutation linked with familial atrial fibrillation.

A frameshift (fs) mutation in the natriuretic peptide precursor A (NPPA) gene, encoding a mutant atrial natriuretic peptide (Mut-ANP), has been linked with familial atrial fibrillation (AF) but the underlying mechanisms by which the mutation causes AF remain unclear. We engineered 2 transgenic (TG) mouse lines expressing the wild-type (WT)-NPPA gene (H-WT-NPPA) and the human fs-Mut-NPPA gene (H-fsMut-NPPA) to test the hypothesis that mice overexpressing the human NPPA mutation are more susceptible to AF and...

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without an effective pharmaceutical treatment. Genetic studies have proved the involvement of smooth muscle phenotype switch in the development of AAA. The alpha subunit of the heterotrimeric G stimulatory protein (Gsα) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of smooth muscle Gsα in AAA formation remains unknown.

Reduced hybrid/complex N-glycosylation disrupts cardiac electrical signaling and calcium handling in a model of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure, with ~70% of DCM cases considered idiopathic. We showed recently, through genetic ablation of the MGAT1 gene, which encodes an essential glycosyltransferase (GlcNAcT1), that prevention of cardiomyocyte hybrid/complex N-glycosylation was sufficient to cause DCM that led to heart failure and early death. Our findings are consistent with increasing evidence suggesting a link between aberrant glycosylation and heart diseases of acquir...

Cardiac arrhythmias after renal I/R depend on IL-1β.

Cardiac arrhythmias are one of the most important remote complications after kidney injury. Renal ischemia reperfusion (I/R) is a major cause of acute renal injury predisposing to several remote dysfunctions, including cardiac electrical disturbance. Since IL-1β production dependent on NLRP3 represents a link between tissue malfunctioning and cardiac arrhythmias, here we tested the hypothesis that longer ventricular repolarization and arrhythmias after renal I/R depend on this innate immunity sensor.

cAMP/PKA signaling compartmentalization in cardiomyocytes: Lessons from FRET-based biosensors.

3',5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger produced in response to the stimulation of G protein-coupled receptors (GPCRs). It regulates a plethora of pathophysiological processes in different organs, including the cardiovascular system. It is now clear that cAMP is not uniformly distributed within cardiac myocytes but confined in specific subcellular compartments where it modulates key players of the excitation-contraction coupling as well as other processes including gene ...

MiRNA profiling revealed enhanced susceptibility to oxidative stress of endothelial cells from bicuspid aortic valve.

Calcific aortic valve stenosis (CAVS) is the most frequent manifestation of aortic valve disease and the third leading cause of cardiovascular disease in the Western countries associated with significant morbidity and mortality. An active biological progression involving inflammation and oxidation leading to valve endothelial damage is considered a hallmark of the early stages of valve degeneration. However, tricuspid (TAV) and bicuspid (BAV) aortic valve deterioration are considered to differ only by shear...

Critical appraisal of STAT3 pattern in adult cardiomyocytes.

The signal transducer and activator of transcription 3, STAT3, transfers cellular signals from the plasma membrane to the nucleus, acting as a signaling molecule and a transcription factor. Reports proposed an additional n-canical role of STAT3 that could regulate the activity of complexes I and II of the electron transport chain and the opening of the mitochondrial permeability transition pore (PTP) after ischemia-reperfusion in various cell types. The native expression of STAT3 in heart mitochondria, toge...

Knockout of adenylyl cyclase isoform 5 or 6 differentially modifies the β-adrenoceptor-mediated inotropic response.

Although only β-adrenergic receptors (βAR) dually couple with stimulatory G protein (G) and inhibitory G protein (G), inactivation of G enhances both βAR and βAR responsiveness. We hypothesize that G restrains spontaneous adenylyl cyclase (AC) activity independent of receptor activation. Subcellular localization of the AC5/6 subtypes varies contributing to the compartmentation of βAR signaling. The primary objectives were to determine: (1) if βAR-mediated inotropic responses were dependent upon either...

Matrix metalloproteinase-12 produced by Ly6C macrophages prolongs the survival after myocardial infarction by preventing neutrophil influx.

Various immune cells are involved in different phases of cardiac repair after myocardial infarction (MI). Especially, Ly6C M2-like macrophages (Ly6C macrophages) are vital for cardiac repair after MI. However, the molecular mechanisms how Ly6C macrophages promote wound healing after MI are still largely unknown.

The role of fibroblast - Cardiomyocyte interaction for atrial dysfunction in HFpEF and hypertensive heart disease.

Atrial contractile dysfunction is associated with increased mortality in heart failure (HF). We have shown previously that a metabolic syndrome-based model of HFpEF and a model of hypertensive heart disease (HHD) have impaired left atrial (LA) function in vivo (rat). In this study we postulate, that left atrial cardiomyocyte (CM) and cardiac fibroblast (CF) paracrine interaction related to the inositol 1,4,5-trisphosphate signalling cascade is pivotal for the manifestation of atrial mechanical dysfunction i...

Heparanase protects the heart against chemical or ischemia/reperfusion injury.

Although cancer cells use heparanase for tumor metastasis, favourable effects of heparanase have been reported in the management of Alzheimer's disease and diabetes. Indeed, we previously established a protective function for heparanase in the acutely diabetic heart, where it conferred cardiomyocyte resistance to oxidative stress and apoptosis by provoking changes in gene expression. In this study, we tested if overexpression of heparanase can protect the heart against chemically induced or ischemia/reperfu...

Activation of the PP2A catalytic subunit by ivabradine attenuates the development of diabetic cardiomyopathy.

Hyperglycemia-induced apoptosis plays a critical role in the pathogenesis of diabetic cardiomyopathy (DCM). Our previous study demonstrated that ivabradine, a selective I current antagonist, significantly attenuated myocardial apoptosis in diabetic mice, but the underlying mechanisms remained unknown. This study investigated the underlying mechanisms by which ivabradine exerts anti-apoptotic effects in experimental DCM. Pretreatment with ivabradine, but not ZD7288 (an established I current blocker), profoun...

Identification of circumferential regional heterogeneity of ascending thoracic aneurysmal aorta by biaxial mechanical testing.

Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) can present an asymmetrical aortic dilatation compared with patients with tricuspid aortic valve (TAV). This pattern of aneurysm dilatation led us to hypothesize that biomechanical differences likely induced by regional heterogeneity of material properties can underlie the observed asymmetric enlargement discrepancies between BAV ATAA and TAV ATAA. This study aimed to characterize the mechanical properties and associated ...

Yin-Yang 1 transcription factor modulates ST2 expression during adverse cardiac remodeling post-myocardial infarction.

The cardioprotective effects of metformin remain poorly defined. Interleukin (IL)-33/ST2L signaling is a novel cardioprotective pathway, which is antagonized by the soluble isoform sST2. No data exist about the regulation of ST2 expression. This study aimed to evaluate the pathophysiological implication of Yin-Yang 1 (Yy1) transcription factor in cardiac remodeling and the expression of the soluble ST2 isoform.

The assembly and evaluation of antisense oligonucleotides applied in exon skipping for titin-based mutations in dilated cardiomyopathy.

The leading cause of genetic dilated cardiomyopathy (DCM) is due to mutations in the TTN gene, impacting approximately 15-20% of familial and 18% of sporadic DCM cases. Currently, there is potential for a personalized RNA-based therapeutic approach in titin-based DCM, utilizing antisense oligonucleotide (AON) mediated exon-skipping, which attempts to reframe mutated titin transcripts, resulting in shortened, functional protein. However, the TTN gene is massive with 363 exons; each newly identified TTN exon ...

Downregulation of ATR decreases the responsiveness of BK channels to angiotensin II in patients with hypertension.

Angiotensin II (Ang II) modulates blood pressure via Ang II type 1 receptor (ATR) and type 2 receptor (ATR). The activation of ATR relaxes vascular tone through opening large-conductance Ca-activated potassium (BK) channels in vascular smooth muscle cells (SMCs). In the present study, we studied the role of the ATR-BK pathway in patients with hypertension. The mesenteric arterial SMCs (MSMCs) were obtained from normotensive patients (NP) and hypertensive patients (HP). BK currents were recorded with patch c...

Epigenetic therapies in heart failure.

Heart failure (HF) is a dominant cause of morbidity and mortality in the developed world. Currently available pharmacotherapies for HF, which largely comprise blockade of circulating neurohormones, are limited by high rates of residual mortality and do not directly target the fundamental changes in cell state that drive adverse cardiac remodeling. In the context of HF, stress-activated cardiac signaling cascades converge on defined components of the chromatin regulatory apparatus in the nucleus, triggering ...

LncRNA H19 promotes vascular inflammation and abdominal aortic aneurysm formation by functioning as a competing endogenous RNA.

Abdominal aortic aneurysm (AAA) is accepted as a chronic vascular inflammatory disease. However, how the inflammatory response is regulated during AAA formation is not fully understood. This study was undertaken to determine whether the long noncoding RNA (lncRNA) H19 (H19) promotes AAA formation by enhancing aortic inflammation. qRT-PCR detected the upregulation of H19 in human and mouse AAA tissue samples. Co-staining of H19 and macrophage marker MAC-2 showed that H19 was located in vascular smooth muscle...

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