Heme oxygenase-1 and carbon monoxide are key mediators for vascular smooth muscle cells proliferation induced by insulin-like growth factor-I.
- Author:
Da-nan LIU
1
;
Zuo-yun HE
;
Ying FANG
;
Li-rong WU
;
Xing-de LIU
;
Lu YU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Carbon Monoxide; metabolism; Cell Proliferation; Cells, Cultured; Heme Oxygenase-1; metabolism; Insulin-Like Growth Factor I; pharmacology; Muscle, Smooth, Vascular; cytology; Myocytes, Smooth Muscle; cytology; metabolism; RNA, Messenger; genetics; Rabbits
- From: Chinese Journal of Cardiology 2006;34(2):153-158
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSVSMCs 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.
RESULTSThe 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.
CONCLUSIONSEndogenous HO-1 and CO are important mediators for inhibiting IGF-I induced VSMCs proliferation by reducing VSMCs DNA synthesis and decelerating cell cycle progression.
