Short-Term Versus Long-Term Intermittent Hypobaric Hypoxia on Cardiac Fibrosis and Fas Death Receptor Dependent Apoptotic Pathway in Rat Hearts


Yueh-Min Lin;Shu-Kuei Huang;Hsueh-Fang Wang;Li-Mien Chen;Fuu-Jen Tsai;Hsi-Hsien Hsu;Chia-Hua Kuo;Paulus S. Wang;Chih-Yang Huang;Shin-Da Lee

Key Words

cardiac fibrosis ; cell apoptosis ; high altitude ; Fas pathway ; time course


The Chinese Journal of Physiology

Volume or Term/Year and Month of Publication

51卷5期(2008 / 10 / 01)

Page #

308 - 316

Content Language


English Abstract

It is unknown if short-term and long-term intermittent hypobaric hypoxic challenges both exert pro-apoptotic effects on Fas death receptor-dependent apoptotic pathway in rat hearts. Seventy-two Sprague-Dawley rats were randomly assigned into two groups. First, short-term intermittent hypobaric hypoxia (STIHH)-normobaric normoxia (n=12), hypobaric hypoxia (380 mmHg, 12% O2, 8 hrs/day) for 1 day (n=12), and for 4 days (n=12) and second, long-term intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n=12), hypobaric hypoxia for 1 week (n=12) and 2 weeks (n=12). After STIHH or LTIHH challenge, Fas receptor related pathway and histopathological analysis in the excised left ventricle was determined by Western blotting, RT-PCR, Hematoxylin-eosin staining, Masson trichrome staining and TUNEL assay. Fas death receptor and TNFα were significantly decreased after STIHH whereas Fas receptor, TNFα, FAS-associated death domain (FADD), and caspase 8 were increased after LTIHH. In addition, cardiomyocyte disarray and fibrosis were observed in 1 week LTIHH. Cardiac hypertrophy and more severe disarray, fibrosis and cardiac apoptotic activities were observed in 2 week LTIHH. STIHH exerts anti-apoptotic effects on hearts such as downregulation of TNFα and Fas receptor whereas LTIHH exerts pro-apoptotic effects such as upregulation of TNFα and Fas-mediated apoptotic pathways and lead to cardiac fibrosis and apoptosis. Our findings imply that short-term versus long-term intermittent hypobaric hypoxia exerted protective versus deleterious effects on hearts.

Topic Category 醫藥衛生 > 基礎醫學
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