Heme Oxygenase-1 Induced by Aprotinin Inhibits Vascular Smooth Muscle Cell Proliferation Through Cell Cycle Arrest in Hypertensive Rats.
10.4196/kjpp.2009.13.4.309
- Author:
Hyoung Chul CHOI
1
;
Kwang Youn LEE
;
Dong Hyup LEE
;
Young Jin KANG
Author Information
1. Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. yjkang@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Aprotinin;
Hypertension;
Proliferation;
Heme oxygenase-1;
Cell cycle arrest
- MeSH:
Animals;
Aprotinin;
Cell Cycle;
Cell Cycle Checkpoints;
Cell Proliferation;
Cyclin D;
G1 Phase;
Heme;
Heme Oxygenase (Decyclizing);
Heme Oxygenase-1;
Hypertension;
Metalloporphyrins;
Muscle, Smooth, Vascular;
Phosphotransferases;
Protoporphyrins;
Rats;
Tin;
Transfection
- From:The Korean Journal of Physiology and Pharmacology
2009;13(4):309-313
- CountryRepublic of Korea
- Language:English
-
Abstract:
Spontaneous hypertensive rats (SHR) are an established model of genetic hypertension. Vascular smooth muscle cells (VSMC) from SHR proliferate faster than those of control rats (Wistar-Kyoto rats; WKY). We tested the hypothesis that induction of heme oxygenase (HO)-1 induced by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats. Aprotinin treatment inhibited VSMC proliferation in SHR more than in normotensive rats. These inhibitory effects were associated with cell cycle arrest in the G1 phase. Tin protoporphyrin IX (SnPPIX) reversed the anti-proliferative effect of aprotinin in VSMC from SHR. The level of cyclin D was higher in VSMC of SHR than those of WKY. Aprotinin treatment downregulated the cell cycle regulator, cyclin D, but upregulated the cyclin-dependent kinase inhibitor, p21, in VSMC of SHR. Aprotinin induced HO-1 in VSMC of SHR, but not in those of control rats. Furthermore, aprotinin-induced HO-1 inhibited VSMC proliferation of SHR. Consistently, VSMC proliferation in SHR was significantly inhibited by transfection with the HO-1 gene. These results indicate that induction of HO-1 by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats.
