Article

Hemin inhibits hypertensive rat vascular smooth muscle cell proliferation through regulation of cyclin D and p21

Gyeongsang National University Department of Pharmacology Jinju Korea; Yeungnam University Department of Pharmacology and Aging-associated Vascular Disease Research Center Daegu Korea
Archives of Pharmacal Research (Impact Factor: 1.54). 01/2009; 32(3):375-382. DOI: 10.1007/s12272-009-1310-2

ABSTRACT We tested the hypothesis that HO-1 (heme oxygenase-1) activity varied between vascular smooth muscle cells (VSMC) in spontaneously
hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. HO-1 levels were measured under baseline and hemin-stimulated
conditions and cell proliferation was monitored. Basal HO-1 levels in untreated cells were lower in SHR compared to WKY rats.
Treatment with hemin increased HO-1 mRNA and protein levels in the cells obtained from WKY rats compared to that of SHR rats.
However, hemin-treatment showed a greater inhibitory effect on VSMC proliferation in SHR rats than in WKY rats. Tin protoporphyrin
IX (SnPPIX) showed a greater reversal of the anti-proliferative effect of hemin on cells from SHR rats than WKY. Similarly,
VSMC proliferation from SHR was significantly inhibited in VSMC transfected with the HO-1 gene. These inhibitory effects were associated with cell cycle arrest in the G1 phase. The level of cyclin D, and cyclin
dependent kinase inhibitor p21 was higher in SHR cells progressing through the G1 phase. Treatment of the cells with hemin
down-regulated the expression of cyclin D and up-regulated that of p21. These results indicate that hemin, an HO-1 inducer,
may play a more critical role in VSMC proliferation in SHR than WKY.

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