肌肉肥大
心力衰竭
生物
内科学
下调和上调
小RNA
右心室肥大
心脏病学
心室重构
纤维化
左心室肥大
肺动脉
基因
内分泌学
医学
遗传学
血压
作者
Sushma Reddy,Mingming Zhao,Dong‐Qing Hu,Giovanni Fajardo,Shijun Hu,Zhumur Ghosh,Viswanathan Rajagopalan,Joseph C. Wu,Daniel Bernstein
出处
期刊:Physiological Genomics
[American Physiological Society]
日期:2012-03-28
卷期号:44 (10): 562-575
被引量:99
标识
DOI:10.1152/physiolgenomics.00163.2011
摘要
MicroRNAs (miRs) are small, noncoding RNAs that are emerging as crucial regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and failure (LVF). However, there are no data on their role in right ventricular hypertrophy (RVH) and failure (RVF). This is a critical question given that the RV is uniquely at risk in patients with congenital right-sided obstructive lesions and in those with systemic RVs. We have developed a murine model of RVH and RVF using pulmonary artery constriction (PAC). miR microarray analysis of RV from PAC vs. control demonstrates altered miR expression with gene targets associated with cardiomyocyte survival and growth during hypertrophy (miR 199a-3p) and reactivation of the fetal gene program during heart failure (miR-208b). The transition from hypertrophy to heart failure is characterized by apoptosis and fibrosis (miRs-34, 21, 1). Most are similar to LVH/LVF. However, there are several key differences between RV and LV: four miRs (34a, 28, 148a, and 93) were upregulated in RVH/RVF that are downregulated or unchanged in LVH/LVF. Furthermore, there is a corresponding downregulation of their putative target genes involving cell survival, proliferation, metabolism, extracellular matrix turnover, and impaired proteosomal function. The current study demonstrates, for the first time, alterations in miRs during the process of RV remodeling and the gene regulatory pathways leading to RVH and RVF. Many of these alterations are similar to those in the afterload-stressed LV. miRs differentially regulated between the RV and LV may contribute to the RVs increased susceptibility to heart failure.
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