Open AccessProtective effect of HDL on NADPH oxidase-derived super oxide anion mediates hypoxia-induced cardiomyocyte apoptosis
Author(s) -
Song Wen,
Shanmugam Tamilselvi,
Chia Yao Shen,
Cecilia Hsuan Day,
Li Chin Chun,
Li Yi Cheng,
Hsiu Chung Ou,
Ray Jade Chen,
Vijaya Padma Viswanadha,
Wei Wen Kuo,
ChihYang Huang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0179492
Subject(s) - nadph oxidase , hypoxia (environmental) , apoptosis , reactive oxygen species , downregulation and upregulation , microbiology and biotechnology , signal transduction , nox4 , medicine , biology , chemistry , endocrinology , biochemistry , oxygen , organic chemistry , gene
Cardiovascular diseases are the leading cause of death of death in Taiwan. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death. Coronary heart disease (CHD) occurs when plaque builds up in the coronary arteries to cause the ischemic heart disease which will enhance myocardial remodeling and also induce myocardial hypoxia. High density lipoprotein (HDL) has been proposed to have cardio-protective effects. Under hypoxic conditions (1%O 2 for 24hr), in H9c2 cells, reactive oxygen species (ROS) is induced which leads to cardiomyocyte apoptosis and cardiac dysfunction. Therefore, the present study described the protective effect of HDL on hypoxia-induced cardiomyocyte damage. We investigated the NADPH oxidase-produced ROS-related signaling pathways and apoptosis in cardiomyocytes under hypoxia conditions. Results showed that the ROS mediated cardiac damage might occur via AT1 and PKC activation. Furthermore, hypoxia downregulated the survival protein (p-AKT ser473 ) and anti-apoptotic protein (BCL 2 ), whereas pro-apoptotic protein, Bax and caspase 3 were upregulated. These detrimental effects by ROS and apoptosis were prevented by HDL pretreatment. Our findings revealed the underlying molecular mechanism by which HDL suppresses the hypoxia-induced cardiomyocyte dysfunction. Further, we elucidated the role of HDL on preventing hypoxia induced cardiomyocyte apoptosis is mediated through the inhibition of NADPH oxidase-derived ROS.