Int J Biol Sci 2012; 8(10):1431-1446. doi:10.7150/ijbs.4664
Influence of Carbon Monoxide on Growth and Apoptosis of Human Umbilical Artery Smooth Muscle Cells and Vein Endothelial Cells
1. Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Carbon monoxide (CO) is a vasoactive molecule that is generated by vascular cells as a byproduct of heme catabolism and it plays an important physiological role in circulation system. In order to investigate whether exogenous CO can mediate the growth and proliferation of vascular cells, in this study, we used 250 parts per million (ppm) of CO to treat human umbilical artery smooth muscle cell (hUASMC) and human umbilical vein endothelial cell (HuVEC) and further evaluated the growth and apoptosis status of SMC and HuVEC. After SMC and HuVEC were exposed to CO for 7-day, the growth of SMC and HuVEC was significantly inhibited by CO in vitro on day 5 of CO exposure. And CO blocked cell cycle progress of SMC and HuVEC, more SMC and HuVEC stagnated at G0/G1 phase by flow cytometric analysis. Moreover, CO treatment inhibited SMC and HuVEC apoptosis caused by hydrogen peroxide through decreasing caspase 3 and 9 activities. To confirm the molecular mechanism of CO effect on SMC and HuVEC growth, we compared the gene expression profile in SMC and CO-treated SMC, HuVEC and CO-treated HuVEC. By microarray analysis, we found the expression level of some genes which are related to cell cycle regulation, cell growth and proliferation, and apoptosis were changed during CO exposure. We further identified that the down-regulated CDK2 contributed to arresting cell growth and the down-regulated Caspase 3 (CASP3) and Caspase 9 (CASP9) were associated with the inhibition of cell apoptosis. Therefore, CO exerts a certain growth arrest on SMC and HuVEC by inhibiting cell cycle transition from G0/G1 phase to S phase and has regulatory effect on cell apoptosis by regulating the expression of apoptosis-associated genes.
Keywords: CO, smooth muscle cell, human umbilical vein endothelial cell, cell proliferation, apoptosis.
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How to cite this article:
Li Y, Wang H, Yang B, Yang J, Ruan X, Yang Y, Wakeland EK, Li Q, Fang X. Influence of Carbon Monoxide on Growth and Apoptosis of Human Umbilical Artery Smooth Muscle Cells and Vein Endothelial Cells. Int J Biol Sci 2012; 8(10):1431-1446. doi:10.7150/ijbs.4664. Available from http://www.ijbs.com/v08p1431.htm