Short-term versus long-term intermittent hypobaric hypoxia on cardiac fibrosis and Fas death receptor dependent apoptotic pathway in rat hearts.
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 TNFalpha were significantly decreased after STIHH whereas Fas receptor, TNFalpha, 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 TNFalpha and Fas receptor whereas LTIHH exerts pro-apoptotic effects such as upregulation of TNFalpha 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.
Lin
Yueh-Min
YM
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan, Republic of China.
Huang
Shu-Kuei
SK
Wang
Hsueh Fang
HF
Chen
Li-Mien
LM
Tsai
Fuu-Jen
FJ
Hsu
Hsi-Hsien
HH
Kuo
Chia-Hua
CH
Wang
Paulus S
PS
Huang
Chih-Yang
CY
Lee
Shin-Da
SD
D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005355:Fibrosis; D006321:Heart / Q000502:physiology; D000860:Hypoxia / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor