RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy.

Background: The genetic basis of a considerable fraction of hypertrophic cardiomyopathy (HCM) cases remains unknown. Whether the gene encoding RNA binding motif protein 20 (RBM20) is implicated in HCM and the correlation of clinical characteristics of RBM20 heterozygotes with HCM remain unresolved. We aimed to investigate the association between RBM20 variants and HCM.

Ranolazine prevents pressure overload-induced cardiac hypertrophy and heart failure by restoring aberrant Na and Ca handling.

Background: Cardiac hypertrophy and heart failure are characterized by increased late sodium current and abnormal Ca handling. Ranolazine, a selective inhibitor of the late sodium current, can reduce sodium accumulation and Ca overload. In this study, we investigated the effects of ranolazine on pressure overload-induced cardiac hypertrophy and heart failure in mice.

Activation of AMP-activated protein kinase by metformin ablates angiotensin II-induced endoplasmic reticulum stress and hypertension in mice in vivo.

Background And Purpose: Metformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts BP-lowering effects in patients with diabetes. However, the effects and underlying mechanisms of metformin on BP in non-diabetic conditions remain to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo.

Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor-A expression and angiogenesis during cardiac hypertrophy in vivo.

Endoplasmic reticulum (ER) stress has been reported to be involved in many cardiovascular diseases such as atherosclerosis, diabetes, myocardial ischemia, and hypertension that ultimately result in heart failure. XBP1 is a key ER stress signal transducer and an important pro-survival factor of the unfolded protein response (UPR) in mammalian cells. The aim of this study was to establish a role for XBP1 in the deregulation of pro-angiogenic factor VEGF expression and potential regulatory mechanisms in hypertrophic and failing heart.

MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo.

Background: XBP1 is a key transcription factor of the unfolded protein response in mammalian cells, which is involved in several cardiovascular pathological progression including cardiac hypertrophy and myocardial infarction, but its expression trend, function and upstream regulate mechanism in the development of heart failure are unclear. In the present study, therefore, the potential role of miRNAs in the regulation of XBP1 expression in heart failure was examined.

Methods And Results: First, western blots showed that cardiac expression of ER stress marker XBP1 were induced in the early adaptive phase, but decreased in the maladaptive phase in hypertrophic and failing heart, while there was no obvious change of upstream ATF6 and IRE1 activity in this progression.

CYP epoxygenase 2J2 prevents cardiac fibrosis by suppression of transmission of pro-inflammation from cardiomyocytes to macrophages.

Cytochrome P450 epoxygenase (CYP450)-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; but the underlying mechanism remains unclear. The present study aimed to elucidate how EETs regulated cardiac fibrosis in response to isoprenaline (Iso) or angiotensin (Ang) II. Cardiac-specific human CYP2J2 transgenic mice (Tr) and wild-type (WT) C57BL/6 littermates were infused with Iso- or Ang II.

MicroRNA-214 Is Upregulated in Heart Failure Patients and Suppresses XBP1-Mediated Endothelial Cells Angiogenesis.

More and more miRNAs have been shown to regulate gene expression in the heart and dysregulation of their expression has been linked to cardiovascular diseases including the miR-199a/214 cluster. However, the signature of circulating miR-214 expression and its possible roles during the development of heart failure has been less well studied. In this study, we elucidated the biological and clinical significance of miR-214 dysregulation in heart failure.

CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure.

Prolonged endoplasmic reticulum (ER) stress causes apoptosis and is associated with heart failure. Whether CYP2J2 and its arachidonic acid metabolites [epoxyeicosatrienoic acids (EETs)] have a protective influence on ER stress and heart failure has not been studied. Assays of myocardial samples from patients with end-stage heart failure showed evidence of ER stress.

Chronic inhibition of cGMP-specific phosphodiesterase 5 suppresses endoplasmic reticulum stress in heart failure.

Background And Purpose: Inhibition of the cGMP-specific phosphodiesterase 5 (PDE5) exerts profound beneficial effects on failing hearts. However, the mechanisms underlying the therapeutic effects of PDE5 inhibition on heart failure are unclear. The purpose of this study was to investigate whether PDE5 inhibition decreases endoplasmic reticulum (ER) stress, a key event in heart failure.

Endoplasmic reticulum stress participates in aortic valve calcification in hypercholesterolemic animals.

Objectives: Aortic valve (AV) calcification occurs via a pathophysiological process that includes lipoprotein deposition, inflammation, and osteoblastic differentiation of valvular interstitial cells. Here, we investigated the association between endoplasmic reticulum (ER) stress and AV calcification.

Approach And Results: We identified ER stress activation in AV of patients with calcified AV stenosis.

Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction.

Background: MicroRNAs (miRNAs) play key roles in diverse biological and pathological processes, including the regulation of proliferation, apoptosis, angiogenesis and cellular differentiation. Recently, circulating miRNAs have been reported as potential biomarkers for various pathologic conditions. This study investigated miR-30a, miR-195 and let-7b as potential of biomarker for acute myocardial infarction (AMI).

Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling.

Background: Using fatty acids (FAs) exclusively for ATP generation was reported to contribute to the development of diabetic cardiomyopathy. We studied the role of substrate metabolism related genes in the heart of the diabetes to find out a novel therapeutic target for diabetic cardiomyopathy.

Methods And Results: By microarray analysis of metabolic gene expression, acyl-CoA thioesterase 1 (acot1) was clearly upregulated in the myocardia of db/db mice, compared with normal control C57BL/Ks.

Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction.

Circulating miRNAs have been shown as promising biomarkers for various pathologic conditions. The aim of this study was to clarify that circulating miR-1 and miR-126 in human plasma might be useful as biomarkers in acute myocardial infarction (AMI). In our study, after pre-test, two candidate miRNAs were detected by using real-time RT-PCR.

ER stress negatively modulates the expression of the miR-199a/214 cluster to regulates tumor survival and progression in human hepatocellular cancer.

Background: Recent studies have emphasized causative links between microRNAs (miRNAs) deregulation and tumor development. In hepatocellular carcinoma (HCC), more and more miRNAs were identified as diagnostic and prognostic cancer biomarkers, as well as additional therapeutic tools. This study aimed to investigate the functional significance and regulatory mechanism of the miR-199a2/214 cluster in HCC progression.

β-AR blockers suppresses ER stress in cardiac hypertrophy and heart failure.

Background: Long-term β-adrenergic receptor (β-AR) blockade reduces mortality in patients with heart failure. Chronic sympathetic hyperactivity in heart failure causes sustained β-AR activation, and this can deplete Ca(2+) in endoplasmic reticulum (ER) leading to ER stress and subsequent apoptosis. We tested the effect of β-AR blockers on ER stress pathway in experimental model of heart failure.