Li L.,Peking University |
Zhang Z.-G.,Peking University |
Lei H.,Peking University |
Wang C.,Peking University |
And 5 more authors.
PLoS ONE | Year: 2013
Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2) mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII) on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1) receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS) scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII. © 2013 Li et al. Source
Wang C.,Peking University |
Wen J.,China Japan Friendship Hospital |
Zhou Y.,Peking University |
Li L.,Peking University |
And 6 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2015
Apelin is an adipokine that has a critical role in the development of atherosclerosis, which may offer potential for therapy. Because migration of vascular smooth muscle cells (VSMCs) is a key event in the development of atherosclerosis, understanding its effect on the atherosclerotic vasculature is needed. Here we investigated the effect of apelin on VSMC migration and the possible signaling mechanism. In cultured rat VSMCs, apelin dose- and time-dependently promoted VSMC migration. Apelin increased the phosphorylation of Akt, whereas LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), and an Akt1/2 kinase inhibitor blocked the apelin-induced VSMC migration. Apelin dose-dependently induced phosphorylation of Forkhead box O3a (FoxO3a) and promoted its translocation from the nucleus to cytoplasm, which were blocked by LY294002 and Akt1/2 kinase inhibitor. Furthermore, apelin increased matrix metalloproteinase 2 (MMP-2) expression and gelatinolytic activity. Overexpression of a constitutively active, phosphorylation-resistant mutant, TM-FoxO3a, in VSMCs abrogated the effect of apelin on MMP-2 expression and VSMC migration. ARP101, an inhibitor of MMP-2, suppressed apelin-induced VSMC migration. Moreover, the levels of apelin, phosphorylated Akt, FoxO3a, and MMP-2 were higher in human carotid-artery atherosclerotic plaque than in adjacent normal vessels. We demonstrate that PI3K/Akt/FoxO3a signaling may be involved in apelin inducing VSMC migration. Phosphorylation of FoxO3a plays a central role in mediating the apelin-induced MMP-2 activation and VSMC migration. © 2015 Published by Elsevier Ltd. Source
Chen S.,Peking University |
Chen B.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
Nie Y.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
Feng X.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
And 3 more authors.
National Medical Journal of China | Year: 2015
Objective To explore the relationship between ambulatory blood pressure and myocardial performance index (MPI) in hypertensive patients. Methods A total of 76 hospitalized patients with untreated hypertension from January to June 2013 were recruited. They received the examinations of office blood pressure, 24 h ambulatory blood pressure and echocardiography. MPI was determined by the following formula: MPI = (isovolumic contraction time + isovolumic relaxation time)/ejection time. Based upon left ventricular MPI, they were divided into two groups of MPI > 0.47 (n = 38) and MPI ≤0.47 (n = 38). The mean levels of office blood pressure, ambulatory blood pressure, blood pressure load, morning blood pressure surge (early morning blood pressure minus the lowest night-time blood pressure) and nocturnal blood pressure changes were compared between two groups. And the determinants of MPI were identified by multivariate regression analysis. Results As compared to those with MPI ≤0.47, patients with MPI > 0.47 had higher 24 h and daytime systolic blood pressures, 24 h, daytime and nighttime diastolic blood pressures, 24 h, daytime and nighttime systolic blood pressure loads, 24 h, daytime and nighttime diastolic blood pressure loads and morning systolic blood pressure surges (all P < 0.05). No inter-group ditferences existed in the mean levels of office blood pressure, nighttime systolic blood pressure, morning diastolic blood pressure surge, nocturnal systolic or diastolic blood pressure changes (all P > 0.05). Multivariate regression analysis showed that nocturnal diastolic blood pressure (β = 0.285, P = 0.005) and daytime systolic blood pressure load (β =0.397, P <0.001) were independently associated with MPI. And other factors independently associated with MPI were left ventricular mass index (LVMI) and early diastolic mitral annular velocity (Em). Conclusion The increases of blood pressure level and blood pressure load are associated with an elevation of left ventricular MPI. Source
Zuo B.,Peking University |
Zuo B.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
Wang F.,Peking University |
Wang F.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
And 6 more authors.
Current Medical Research and Opinion | Year: 2015
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. Pooled risk ratio, mean, standard deviation and 95% CI were used to assess the effect by fixed- or random-effect models. Heterogeneity was assessed by the Cochran Q and I 2 statistics. Results: Nine trials were included in this study. RIC decreased the AKI incidence in patients undergoing PCI compared with control individuals (P<0.001; RR, 0.53; 95% CI, 0.39-0.71; P for heterogeneity=0.15; heterogeneity X2=13.38; I2=33%). Besides, limb conditioning attenuated AKI (P=0.001; RR, 0.57; 95% CI, 0.41-0.81; P for heterogeneity=0.13; heterogeneity X2=12.48; I2=36%). Remote postconditioning may reduce the AKI incidence (P=0.03; RR, 0.65; 95% CI, 0.44-0.97; P for heterogeneity=0.15; heterogeneity X2=5.36; I2=44%); remote preconditioning could also play a renoprotective role (P<0.001; RR, 0.42; 95% CI, 0.27-0.65; P for heterogeneity=0.31; heterogeneity X2=5.98; I2=16%). Conclusions: RIC may not only confer cardioprotection, but also reduce the incidence of AKI in patients undergoing PCI, ultimately leading to better clinical outcomes. RIC may potentially be a powerful approach conferring protection in patients undergoing PCI in future clinical practice. More large-scale trials are required to obtain a more reliable conclusion. © 2015 Informa UK Ltd. Source
Wang J.,Beijing Institute of Biotechnology |
Song Y.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
Zhang Y.,Beijing Institute of Biotechnology |
Xiao H.,Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides |
And 13 more authors.
Cell Research | Year: 2012
Recent studies have begun to reveal critical roles of microRNAs (miRNAs) in the pathogenesis of cardiac hypertrophy and dysfunction. In this study, we tested whether a transforming growth factor-β (TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure (HF). We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice, which developed cardiac hypertrophy. In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth, while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine (PE) treatment. Furthermore, the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction. We validated the peroxisome proliferator-activated receptor-γ (PPAR-γ) as a direct target of miR-27b in cardiomyocyte. Consistently, the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice. Furthermore, in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression, attenuated cardiac hypertrophy and dysfunction. The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy, and validate miR-27b as an efficient therapeutic target for cardiac diseases. © 2012 IBCB, SIBS, CAS All rights reserved. Source