Heart failure (HF) is a complex clinical syndrome, characterized by inadequate blood perfusion of tissues and organs caused by decreased heart ejection capacity resulting from structural or functional cardiac disorders. HF is the most severe heart condition and it severely compromises human health; thus, its early diagnosis and effective management are crucial. However, given the lack of satisfactory sensitivity and specificity of the currently available biomarkers, the majority of patients with HF are not diagnosed early and do not receive timely treatment. A number of studies have demonstrated that peripheral blood circulating nucleic acids [such as microRNAs (miRs), mRNA and DNA] are important for the diagnosis and monitoring of treatment response in HF. miRs have been attracting increasing attention as promising biomarkers, given their presence in body fluids and relative structural stability under diverse conditions of sampling. The aim of the present review was to analyze the associations between the mechanisms underlying the development of HF and the expression of miRs, and discuss the value of using circulating miRs as diagnostic biomarkers in HF management. In particular, miR-155, miR-22 and miR-133 appear to be promising for the diagnosis, prognosis and management of HF patients.
We evaluated the neuroprotective effects of atorvastatin (2, 5, and 10 mg/kg) on experimentally induced intracerebral hemorrhage (ICH) in adult rats; controls were administered PBS. Plasma TNF-α and IL-10 levels before and after ICH were analyzed at various time points by enzyme-linked immunosorbent assay (ELISA) and neurological behavior of rats was assessed by climbing scores. At 3-days postoperatively, brain water contents and TNF-α/IL-10 expression in brain tissue were determined. Histopathological changes and microglial cells in the brain tissue were evaluated by light-microscopy. Post-ICH neurological deficits differed significantly between sham-operated group A and experimental-ICH group B (P < 0.05). Brain water contents were significantly less in group A than in group B (P < 0.05). Significant differences (P < 0.05) between two groups were observed regarding activated microglia, TNF-α and IL-10 levels. Compared with group B, neurological deficits, brain water contents, pathological changes, and activated microglia were reduced (P < 0.05) in groups C (Experimental-ICH + atorvastatin 2 mg/kg), D (Experimental-ICH + atorvastatin 5 mg/kg) and E (Experimental-ICH + atorvastatin 10 mg/kg). Atorvastatin-induced a dose-dependent reduction of TNF-α and increase of IL-10 levels (P < 0.05). Therefore, it was concluded that atorvastatin improved neurofunctional rehabilitation in rats through the suppression of cytokines-mediated inflammatory response and attenuation of brain damage following intracerebral hemorrhage.
The vasoconstriction is attenuated in aortic rings from Sm22α(-/-) mice. MKP3 mediates dephosphorylation of ERK1/2 in AngII-induced VSMC contraction. SM22α inhibits the interaction of ERK1/2 with MKP3. SM22α promotes ubiquitination and degradation of MKP3. SM22α facilitates AngII-induced contraction by maintenance of ERK1/2 signaling.
TEG results have important clinical implications in the early diagnosis of acute cerebral infarction.
Aims Smooth muscle 22-alpha (SM22α) is an actin-binding protein that plays critical roles in mediating polymerization of actin filaments and stretch sensitivity of cytoskeleton in vascular smooth muscle cells (VSMCs). Multiple lines of evidence indicate the existence of SM22α in cardiomyocytes. Here, we investigated the effect of cardiac SM22α on the membrane architecture and functions of cardiomyocytes to pressure overload. Methods SM22α knock-out (KO) mice were utilized to assess the role of SM22α in the heart. Echocardiography was used to evaluate cardiac function, transverse aortic constriction (TAC) was used to induce heart failure, cell shortening properties were measured by IonOptix devices in intact cardiomyocytes, Ca2+ sensitivity of myofilaments was measured in permeabilized cardiomyocytes. Confocal microscopy, electron microscopy, western blotting, co-immunoprecipitation (co-IP), Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) techniques were used to perform functional and structural analysis. Results SM22α ablation did not alter cardiac function at baseline, but mRNA levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were increased significantly compared with wild type (WT) controls. The membrane architecture was severely disrupted in SM22α KO cardiomyocytes, with disassembly and flattening of caveolae and disrupted T-tubules. Furthermore, SM22α was co-immunoprecipitated with caveolin-3 (Cav3), and the interaction between Cav3 and actin was significantly reduced in SM22α KO cells. SM22α KO cardiomyocytes displayed asynchronized SR Ca2+ release, significantly increased Ca2+ spark frequency. Additionally, the kinetics of sarcomere shortening was abnormal, accompanied with increased sensitivity and reduced maximum response of myofilaments to Ca2+ in SM22α KO cardiomyocytes. SM22α KO mice were more prone to heart failure after TAC. Conclusions Our findings identified that SM22α may be required for the architecture and function of caveolae and T-tubules in cardiomyocytes.
The mechanism involved in the endotoxin‐induced myocardial dysfunction is not fully understood. The purpose of the present study was to demonstrate that myocardial dysfunction in endotoxinemia is mediated via an increase in myocyte production of high mobility group box 1 protein (HMGB1). In vivo, mouse model of endotoxinemia in mice was induced by i.p. injection of LPS (10 mg/kg) and myocardial function was evaluated 24 hrs later. LPS induced a decrease in myocardial contractility (end‐systolic and end‐diastolic volume relation). The decrease in myocardial contractility was diminished when the mice were received either a HMGB1 antagonist (A‐box) or an inhibitor of HMGB1 (glycyrrhizic acid). Expression of myocardial HMGB1 was increased in the heart of mice treated with LPS (immunoflorescence staining). Further, recombinant HMGB1 (10–20 μg/mouse, i.p.) resulted in a dose dependent decrease in myocardial contractility. To confirm that the source of HMGB1 was the cardiac myocytes in the hearts, isolated cardiac myocytes were exposed to LPS (10 μg/ml). Treatment of cardiac myocytes with LPS increased in intracellular levels of HMGB1 and release HMGB1 by myocytes to the supernatant (Western). Taken together, our study suggests LPS‐induced myocardial dysfunction is a result of increase in myocyte HMGB1. (CIHR MOP 81303).
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