Hypoxia-induced compensatory effect as related to Shh and HIF-1alpha in ischemia embryo rat heart.
Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1alpha and Shh. The relationship between HIF-1alpha and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1alpha signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1alpha and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.
Hwang
Jin-Ming
JM
School of Applied Chemistry, Chung-Shan Medical University, Taichung, Taiwan.
Weng
Yi-Jiun
YJ
Lin
James A
JA
Bau
Da-Tian
DT
Ko
Fu-Yang
FY
Tsai
Fuu-Jen
FJ
Tsai
Chang-Hai
CH
Wu
Chieh-Hsi
CH
Lin
Pei-Cheng
PC
Huang
Chih-Yang
CY
Kuo
Wei-Wen
WW
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D006321:Heart / Q000196:embryology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D053823:Hedgehog Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017451:Receptors, Somatomedin; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II