miR-133: A Suppressor of Cardiac Remodeling?

Cardiac remodeling, which is characterized by mechanical and electrical remodeling, is a significant pathophysiological process involved in almost all forms of heart diseases. MicroRNAs (miRNAs) are a group of non-coding RNAs of 20–25 nucleotides in length that primarily regulate gene expression by promoting mRNA degradation or post-transcriptional repression in a sequence-specific manner. Three miR-133 genes have been identified in the human genome, miR-133a-1, miR-133a-2, and miR-133b, which are located on chromosomes 18, 20, and 6, respectively. These miRNAs are mainly expressed in muscle tissues and appear to repress the expression of non-muscle genes. Based on accumulating evidence, miR-133 participates in the proliferation, differentiation, survival, hypertrophic growth, and electrical conduction of cardiac cells, which are essential for cardiac fibrosis, cardiac hypertrophy, and arrhythmia. Nevertheless, the roles of miR-133 in cardiac remodeling are ambiguous, and the mechanisms are also sophisticated, involving many target genes and signaling pathways, such as RhoA, MAPK, TGFβ/Smad, and PI3K/Akt. Therefore, in this review, we summarize the critical roles of miR-133 and its potential mechanisms in cardiac remodeling

Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases

The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.</jats:p

Cellular repressor of E1A-stimulated genes attenuates cardiac hypertrophy and fibrosis

Cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over-expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase 1 (MEK-ERK1)/2-dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK-ERK1/2-dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK-ERK1/2-dependent signalling

Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schzophrenia revealed by rFMRI

Context Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural systemeffects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophreniabefore and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments. Objective To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episodeschizophrenia before and after treatment with second-generation antipsychotic medication. Design Case-control study. Setting Huaxi MR Research Center and Mental Health Centre of the West China Hospital. Participants Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echoecho-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-fourmatched healthy control subjects were studied at baseline for comparison purposes. Main Outcome Measures The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level–dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration. Results After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF. Conclusions We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs

Loss of Regulator of G Protein Signaling 5 Exacerbates Obesity, Hepatic Steatosis, Inflammation and Insulin Resistance

BACKGROUND: The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF). METHODOLOGY/PRINCIPAL FINDINGS: Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance

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The supplementary data of "Cardiomyocyte specific RIP2 overexpression exacerbate malignant remodeling via promoting TAK1 signaling in vivo and in vitro"</b