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

《The Chinese Journal of Physiology》 51卷5期 (2008/10) Pp. 308-316

並列摘要

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.

並列關鍵字

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

參考文獻

Jong, G.P.,Ma, T.,Chou, P.,Chang, M.H.,Wu, C.H.,Lis, P.C.,Lee, S.D.,Liu, J.Y.,Kuo, W.W.,Huang, C.Y.(2006).Serum MMP-9 activity as a diagnosing marker for the developing heart failure of post MI patients.Chinese J. Physiol..49,104-109.

Abbate, A.,Biondi-Zoccai, G.G.,Baldi, A.,Trani, C.,Biasucci, L.M.,Vetrovec, G.W.(2003).The `Open-Artery Hypothesis`: new clinical and pathophysiologic insights.Cardiology.100,196-206.

Anversa, P.,Nadal-Ginard, B.(2002).Myocyte renewal and ventricular remodelling.Nature.415,240-243.

Biondi-Zoccai, G.G.,Abbate, A.,Vasaturo, F.,Scarpa, S.,Santini, D.,Leone, A.M.,Parisi, Q.,De Giorgio, F.,Bussani, R.,Silvestri, F.,Baldi, F.,Biasucci, L.M.,Baldi, A.(2004).Increased apoptosis in remote non-infarcted myocardium in multivessel coronary disease.Int. J. Cardiol..94,105-110.

Bishopric, N.H.,Andreka, P.,Slepak, T.,Webster, K.A.(2001).Molecular mechanisms of apoptosis in the cardiac myocyte.Curr. Opin. Pharmacol..1,141-150.