LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats.
LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats.
复制标题
LOX-1 促进缺氧大鼠的右心室肥厚。
DOI：
10.1016/j.lfs.2017.02.016
复制
发表时间：
2017
期刊：
影响因子：
6.1
通讯作者：
Hu Chang-Ping
中科院分区：
文献类型：
--
作者：
Zhu Tian-Tian;Zhang Wei-Fang;Luo Ping;Qian Zhao-Xin;Li Feng;Zhang Zheng;Hu Chang-Ping
AimChronic hypoxia leads to right ventricular hypertrophy (RVH). RVH is believed to result from hypoxia-induced pulmonary hypertension. However, if hypoxia impacts RVH directly awaits clarification. Hypoxia triggers oxidative stress, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates reactive oxygen species (ROS) generation in different cells. Therefore, this study aims to explore whether LOX-1-mediated oxidative stress accounts for hypoxia-induced RVH.Main methodsRats developed RVH after 3 weeks of hypoxia (10% O2). Immunofluorescence staining was performed to evaluate H9C2 cell hypertrophy induced by hypoxia (3% O2). Real-time PCR and Western-blot were performed to assess LOX-1, NADPH oxidases (NOX), collagen I/III, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) expression. DCFH-DA staining was performed to measure ROS generation.Key findingsHypoxia induced RVH and cardiac fibrosis in rats, as indicated by enlarged cardiomyocytes and deposition of extracellular matrix. Interestingly, hypoxia treatment directly induced H9C2 cardiomyocyte hypertrophy, implying direct effects of hypoxia on cell hypertrophy. Rat and H9C2 hypertrophy model revealed that cell hypertrophy was accompanied by marked increase in LOX-1 expression. Knockdown of LOX-1 significantly ameliorated H9C2 cell hypertrophy. Mechanistically, hypoxia induced prominent oxidative stress in rat right ventricles and H9C2 cells, most likely as a result from increased expression of NOX2/4, contributing to RVH. Knockdown of LOX-1 significantly attenuated H9C2 cell oxidative stress, with a concomitant decrease in NOX2/4 expression.SignificanceLOX-1/NOX/ROS pathway could represent a novel mechanism underlying hypoxia-induced RVH. Therapeutic targeting of LOX-1 would be exploited to treat RVH owing to chronic hypoxia exposure.
