Deficiency Caused Restrictive Cardiomyopathy via Disrupting Proteostasis.

The molecular mechanisms underlying restrictive cardiomyopathy (RCM) are not fully understood. Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) is a vital element of Endosomal sorting required for transport (ESCRT), which mediates protein sorting for degradation and is crucial for protein homeostasis (proteostasis) maintenance. However, the physiological function and underlying mechanisms of HGS in RCM are unexplored.

Kindlin-2 suppresses transcription factor GATA4 through interaction with SUV39H1 to attenuate hypertrophy.

Kindlin-2 plays an important role in the regulation of cardiac structure and function. Depletion of Kindlin-2 contributes to cardiac hypertrophy and progressive heart failure, however, the precise mechanisms involved in this process remain unclear. GATA4 is a critical transcription factor in regulating cardiogenesis.

Depletion of Kindlin-2 induces cardiac dysfunction in mice.

Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc.

The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy.

Aims: The H19 lncRNA, a highly abundant and conserved imprinted gene, has been implicated in many essential biological processes and diseases. However, the function of H19 in the heart remains unknown. In this study, we investigated the function and underlying mechanism of H19 in regulating cardiomyocyte hypertrophy.

miR-199-sponge transgenic mice develop physiological cardiac hypertrophy.

Aims: Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance.

Methods And Results: We generated a sponge transgenic mouse model with a specific disruption of miR-199 in the heart.

Smad4 Deficiency in Smooth Muscle Cells Initiates the Formation of Aortic Aneurysm.

Rationale: Aortic aneurysm is a life-threatening cardiovascular disorder caused by the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor-β (TGF-β) pathway in aortic aneurysm. Smad4 is the central mediator of the canonical TGF-β signaling pathway.

miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation.

Basal autophagy is tightly regulated by transcriptional and epigenetic factors to maintain cellular homeostasis. Dysregulation of cardiac autophagy is associated with heart diseases, including cardiac hypertrophy, but the mechanism governing cardiac autophagy is rarely identified. To analyze the in vivo function of miR-199a in cardiac autophagy and cardiac hypertrophy, we generated cardiac-specific miR-199a transgenic mice and showed that overexpression of miR-199a was sufficient to inhibit cardiomyocyte autophagy and induce cardiac hypertrophy in vivo.

Using remote ischemic conditioning to reduce acute kidney injury in patients undergoing percutaneous coronary intervention: a meta-analysis.

Background And Aims: It remains uncertain whether remote ischemic conditioning (RIC) could prevent acute kidney injury (AKI) in patients undergoing percutaneous coronary intervention (PCI). Thus, this meta-analysis aiming to explore the renoprotective role of RIC in patients undergoing PCI was carried out.

Methods: PubMed, Web of Science, and Cochrane Library were searched from inception to 31 December 2014 to identify eligible randomized controlled trials.

NEXN inhibits GATA4 and leads to atrial septal defects in mice and humans.

Aims: Cardiac structural genes have been implicated as causative factors for congenital heart diseases (CHDs). NEXN is an F-actin binding protein and previously identified as a disease gene causing cardiomyopathies. Whether NEXN contributes to CHDs aetiologically remains unknown.

Beta-adrenoceptor signaling pathways mediate cardiac pathological remodeling.

Beta-adrenoceptors (ARs), members of the G protein-coupled receptor (GPCR) superfamily, play a key role in the rapid regulation of myocardial function. Meanwhile, chronic catecholamine stimulation of adrenoceptors has been proved to be involved in the adverse myocardial remodeling, including cardiac hypertrophy, fibrosis, and apoptosis, which finally develop into heart failure. In the clinical situation, sympathetic hyperactivity is a key factor in the development of heart failure, and beta-blockers greatly improve the outcome of the disease.

Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation.

Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.

Methods: Wild type and AMPKα2 knockout (AMPKα2⁻/⁻) littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin (200 mg·kg⁻¹·d⁻¹) for 6 weeks, the degree of cardiac hypertrophy was evaluated using echocardiography and anatomic and histological methods.

Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy.

Background And Objectives: Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway.

Developmental changes in the geometry, function and responsiveness of the mouse heart to beta-adrenergic stimulation as determined by high-resolution echocardiography.

1. The mouse is the preferred species for gene targeting as a tool for research into the heart and heart development. The developmental features of the geometry and function of the heart in young mice are not well defined and cardiac functional responses following stimulation of beta-adrenoceptors have not been investigated.

Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy.

Pathophysiological cardiac hypertrophy is one of the most common causes of heart failure. Epoxyeicosatrienoic acids, hydrolyzed and degraded by soluble epoxide hydrolase (sEH), can function as endothelium-derived hyperpolarizing factors to induce dilation of coronary arteries and thus are cardioprotective. In this study, we investigated the role of sEH in two rodent models of angiotensin II (Ang II)-induced cardiac hypertrophy.

[Role of GATA-4 in cardiac development and remodeling].

GATA-4 plays important roles in the process of cardiac development and remodeling. Deletion or mutation of GATA-4 is associated with malformation of cardiac development directly, even embryolethality. Down-regulation of GATA-4 may lead to deterioration of cardiac function.

The gp130/STAT3 signaling pathway mediates beta-adrenergic receptor-induced atrial natriuretic factor expression in cardiomyocytes.

beta-Adrenergic receptor (beta-AR)-induced cardiac remodeling is closely linked with the re-expression of the atrial natriuretic factor (ANF) gene. However, the exact molecular mechanism of this response remains elusive. Here, we demonstrate that the beta-AR agonist isoproterenol potently evokes the tyrosine phosphorylation of STAT3 and increases its transcriptional activity in an extracellularly regulated kinase 1/2 and glycoprotein (gp)130 signaling-dependent manner in rat cardiomyocytes.

Understanding the role of transforming growth factor-beta signalling in the heart: overview of studies using genetic mouse models.

1. In the present review, we focus on the genetic mouse models for transforming growth factor (TGF)-beta signalling, which have aided our understanding on the role of the TGF-beta signalling pathway in cardiac hypertrophy/fibrosis and the molecular mechanisms involved. 2.

Inhibitory crosstalk between ERK and AMPK in the growth and proliferation of cardiac fibroblasts.

Extracellular signal-regulated kinase (ERK) is one of the key protein kinases that regulate the growth and proliferation in cardiac fibroblasts (CFs). As an energy sensor of cellular metabolism, AMP-activated protein kinase (AMPK) is found recently to be involved in myocardial remodeling. In this study, we investigated the crosstalk between ERK and AMPK in the growth and proliferation of CFs.

[Intracoronary transfer autologous bone marrow stem cells can improve cardiac function in patients with left ventricular dysfunction after myocardial infarction].

Objective: To evaluate the efficacy of intracoronary transfer of autologous bone marrow mononuclear stem cells in patients with heart dysfunction after myocardial infarction.

Methods: Forty-two patients with anterior myocardial infarction [BMSC(bone marrow mononuclear stem cells) group: 13 cases; control group: 29 cases] were treated by standard percutaneous coronary intervention (PCI) and medical therapy. Patients in BMSC group were also transplanted bone marrow mononuclear stem cells through coronary injection.

[Isoproterenol regulates lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production in monocytes from essential hypertensive patients.].

Objective: To investigate the effects of beta-adrenoceptor agonist isoproterenol(ISO) on lipopolysaccharide(LPS) induced inflammatory cytokine-tumor necrosis factor-alpha(TNF-alpha) and interleukin-6(IL-6)] in monocytes from essential hypertensive patients (Stage I).

Methods: Monocytes were isolated from 17 healthy volunteers and 6 hypertensive patients' venus blood, and the monocytes were cultured with LPS (0.2 microg/L) and ISO.

alpha1-adrenergic receptors activate AMP-activated protein kinase in rat hearts.

To test the hypothesis that AMP-activated protein kinase (AMPK) is possibly the downstream signaling molecule of certain subtypes of adrenergic receptor (AR) in the heart, we evaluated AMPK activation mediated by ARs in H9C2 cells, a rat cardiac source cell line, and rat hearts. The AMPK-alpha subunit and the phosphorylation level of Thr(172)-AMPK-alpha subunit were subjected to Western blot analysis. Osmotic minipumps filled with norepinephrine (NE), phenylephrine (PE) or vehicle [0.

Internalization and distribution of three alpha1-adrenoceptor subtypes in HEK293A cells before and after agonist stimulation.

Aim: To examine the subcellular distribution of the 3 alpha1-adrenoceptor (alpha1-AR) subtypes and their internalization and trafficking upon agonist stimulation in human embryonic kidney 293A cells.

Methods: Confocal real-time imaging, enzyme linked immunosorbent assay (ELISA) and whole cell [3H]-prazosin binding assay were applied to detect the distribution and localization of the 3 alpha1-AR subtypes.

Results: alpha1A-AR was found both on the cell surface and in the cytoplasm; alpha1BAR, however, was predominantly detected on the cell surface, while alpha1D-AR was detected mainly in the intracellular compartments.

Phenylarsine oxide inhibited beta-adrenergic receptor-mediated IL-6 secretion: inhibition of cAMP accumulation and CREB activation in cardiac fibroblasts.

As we previously reported, cAMP and p38 MAPK instead of protein kinase A were involved in beta-adrenergic receptor (beta-AR)-mediated interleukin-6 (IL-6) production in mouse cardiac fibroblasts. Besides kinases, phosphatases may also be involved in IL-6 gene regulation. To study the role of protein tyrosine phosphatases (PTPs) in beta-AR-mediated IL-6 production, we selected the most widely used PTP inhibitor, phenylarsine oxide (PAO).

[Redistribution of three alpha1-adrenergic receptor subtypes in the stably transfected HEK 293A cells upon agonist stimulation.].

To investigate the subcellular distribution of three alpha(1)-adrenergic receptor subtypes and their internalization and trafficking upon agonist stimulation in human embryonic kidney (HEK) 293A cell line, saturation radioligand binding assay, laser confocal imaging, and Western blot were applied to examine the distribution and changes in localization of three alpha(1)-AR subtypes in transfected HEK 293A cells prior to and after treatment with phenylephrine. The results are as follows: (1) The transfection efficiency was over 90%and was equal among three alpha(1)-AR subtypes. alpha(1B ) -AR expression in cell membrane was the highest, and alpha(1D ) -AR was the lowest, as determined by (125)I-BE2254 binding assay, however, K(d)s were not significantly different among the three receptor subtypes.