Protective effect of HDL on NADPH oxidase-derived super oxide anion mediates hypoxia-induced cardiomyocyte apoptosis

Su Ying 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, Chih Yang Huang

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2 Citations (Scopus)

Abstract

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%O2 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-AKTser473) and anti-apoptotic protein (BCL2), 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.

Original languageEnglish
Article numbere0179492
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Wen, S. Y., Tamilselvi, S., Shen, C. Y., Day, C. H., Chun, L. C., Cheng, L. Y., Ou, H. C., Chen, R. J., Viswanadha, V. P., Kuo, W. W., & Huang, C. Y. (2017). Protective effect of HDL on NADPH oxidase-derived super oxide anion mediates hypoxia-induced cardiomyocyte apoptosis. PLoS One, 12(6), [e0179492]. https://doi.org/10.1371/journal.pone.0179492