[Heme oxygenase-1 and carbon monoxide are key mediators for vascular smooth muscle cells proliferation induced by insulin-like growth factor-I].
OBJECTIVE
To determine the role and related mechanisms of heme oxygenase-1/carbon monoxide (HO-1/CO) on VSMCs proliferation induced by insulin-like growth factor-I (IGF-I).


METHODS
VSMCs isolated from rabbit aorta were cultured in vitro and proliferation was induced by IGF-I. Hemin (a substrate and inducer of HO-1) or zinc protoporphyrin-IX (Znpp-IX, an inhibitor of HO-1) was added to stimulate or inhibit the expression of HO-1. The mRNA and protein expressions of HO-1 were detected by RT-PCR and Western blot analysis. CO released into the culture media was quantitated by measuring carbon monoxide hemoglobin (COHb), VSMCs proliferation and cell cycle were determined by (3)H-TdR incorporation assay and flow cytometry, respectively.


RESULTS
The HO-1 mRNA and protein expressions in VSMCs and the amount of COHb in the culture media were significantly increased and the IGF-I-induced (3)H-TdR incorporations of VSMCs significantly reduced by hemin in a dose-dependent manner (P < 0.01). Furthermore, VSMCs in the G(0)/G(1) phase were increased and in the S and G(2)/M phase decreased by hemin (P < 0.01). Opposite results were observed in VSMCs treated with Znpp-IX.


CONCLUSIONS
Endogenous HO-1 and CO are important mediators for inhibiting IGF-I induced VSMCs proliferation by reducing VSMCs DNA synthesis and decelerating cell cycle progression.
Liu
Da-nan
DN
Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 40037, China.
He
Zuo-yun
ZY
Fang
Ying
Y
Wu
Li-rong
LR
Liu
Xing-de
XD
Yu
Lu
L
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1