Influence of carbon monoxide on growth and apoptosis of human umbilical artery smooth muscle cells and vein endothelial cells.
Influence of carbon monoxide on growth and apoptosis of human umbilical artery smooth muscle cells and vein endothelial cells.
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DOI：
10.7150/ijbs.4664
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发表时间：
2012
影响因子：
9.2
通讯作者：
Fang X
中科院分区：
文献类型：
--
作者：
Li Y;Wang H;Yang B;Yang J;Ruan X;Yang Y;Wakeland EK;Li Q;Fang X
一氧化碳（Carbon monoxide，CO）是血红素催化剂的副产物，由血管细胞产生，在循环系统中起着重要的生理作用。为了探讨外源性CO是否能介导血管细胞的生长和增殖，本研究采用250 ppm CO处理人脐动脉平滑肌细胞（hUASMC）和人脐静脉内皮细胞（HuVEC），进一步观察SMC和HuVEC的生长和凋亡状态。SMC和HuVEC暴露于CO 7 d后，在暴露第5天，SMC和HuVEC的生长受到明显抑制。流式细胞仪分析显示，CO可阻断SMC和HuVEC的细胞周期进程，使更多的SMC和HuVEC停滞在G 0/G1期。CO处理还可通过降低caspase 3和caspase 9的活性来抑制H2 O2诱导的SMC和HuVEC凋亡。为了进一步证实CO影响SMC和HuVEC生长的分子机制，我们比较了SMC和CO处理的SMC、HuVEC和CO处理的HuVEC中的基因表达谱。通过基因芯片分析，我们发现与细胞周期调控、细胞生长增殖和凋亡相关的基因表达水平在CO暴露过程中发生了变化。我们进一步确定下调的CDK 2有助于阻止细胞生长，下调的Caspase 3（CASP 3）和Caspase 9（CASP 9）与细胞凋亡的抑制有关。因此，CO通过抑制细胞周期由G 0/G1期向S期的转变，对SMC和HuVEC产生一定的生长阻滞作用，并通过调节凋亡相关基因的表达，对细胞凋亡具有调节作用。
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.
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影响因子：
4.8
作者：
Conant, K;St Hillaire, C;Nath, A
通讯作者：
Nath, A
影响因子：
20.1
作者：
Ishikawa, K;Sugawara, D;Lusis, AJ
通讯作者：
Lusis, AJ
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR
影响因子：
6.4
作者：
Hirata, Hiroshi;Hinoda, Yuji;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
DOI：
10.1073/pnas.080064097
发表时间：
2000-04-11
影响因子：
11.1
作者：
Lu, JR;McKinsey, TA;Olson, EN
通讯作者：
Olson, EN