Article

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

Yeungnam University Department of Pharmacology and Aging-associated Vascular Disease Research Center Daegu Korea
Archives of Pharmacal Research (Impact Factor: 1.75). 03/2009; 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.

0 Bookmarks
 · 
148 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PPARγ is a member of the nuclear hormone receptor superfamily. It has been considered as a mediator regulating metabolism, anti-inflammation, and pro-proliferation in the Vascular Smooth Muscle Cells (VSMCs). Thiazolidinediones (TZDs), synthetic ligands of PPARγ, have anti-proliferative and pro-apoptotic effects on VSMCs, which prevent the formation and progression of atherosclerosis and restenosis following percutaneous coronary intervention (PCI). However, the underlying mechanism remains elusive. This present study therefore aimed to investigate the signaling pathway by which pioglitazone, one of TZDs, inhibits proliferation and induces apoptosis of VSMCs.
    Diabetology and Metabolic Syndrome 01/2014; 6(1):101. DOI:10.1186/1758-5996-6-101 · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abundant and less passaged cells are highly expected in clinical application since repeated subculture reduces stem cell characteristics. Long time culture of stem cells without passage is therefore needed. The growth and cell viability of human adipose-derived stem cells (hADSCs) were investigated by live/dead staining, cck-8 kits, and hemocytometer every day in 30 days of culture. The stem cell characteristics of hADSCs at the beginning and the end of culture were detected by flow cytometry and histochemical staining. hADSCs can be cultured up to the 30th day in one passage while maintaining high level cell viability and their stem cell characteristics. In addition, the cells displayed two plateau phases and three logarithmic phases during 1 month of culture. Increasing expression of cyclin A at protein level resulted in an increase in the percentage of hADSCs in the S and G(2)/M phases, while decreasing protein level of cyclin D1 induced a decline in the proportion of hADSCs in the G(0)/G(1) phase, regulating cells to move into rapid proliferation. This study demonstrates that a great quantity of hADSCs can be obtained in vitro by prolonging the culture time of each passage. And cyclin A and cyclin D1 affect the distribution of cell cycle and regulate the growth of hADSCs.
    Applied biochemistry and biotechnology 10/2012; DOI:10.1007/s12010-012-9932-0 · 1.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we evaluate the effect of HO-1 upregulation on blood pressure and cardiac function in the new model of infarct spontaneous hypertensive rats (ISHR). Male spontaneous hypertensive rats (SHR) at 13 weeks (n = 40) and age-matched male Wistar (WT) rats (n = 20) were divided into six groups: WT (sham + normal saline (NS)), WT (sham + Co(III) Protoporphyrin IX Chloride (CoPP)), SHR (myocardial infarction (MI) + NS), SHR (MI + CoPP), SHR (MI + CoPP + Tin Mesoporphyrin IX Dichloride (SnMP)), SHR (sham + NS); CoPP 4.5 mg/kg, SnMP 15 mg/kg, for six weeks, one/week, i.p., n = 10/group. At the sixth week, echocardiography (UCG) and hemodynamics were performed. Then, blood samples and heart tissue were collected. Copp treatment in the SHR (MI + CoPP) group lowered blood pressure, decreased infarcted area, restored cardiac function (left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), +dp/dt(max), (-dp/dt(max))/left ventricular systolic pressure (LVSP)), inhibited cardiac hypertrophy and ventricular enlargement (downregulating left ventricular end-systolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and heart weight/body weight (HW/BW)), lowered serum CRP, IL-6 and Glu levels and increased serum TB, NO and PGI2 levels. Western blot and immunohistochemistry showed that HO-1 expression was elevated in the SHR (MI + CoPP) group, while co-administration with SnMP suppressed the benefit functions mentioned above. In conclusion, HO-1 upregulation can lower blood pressure and improve post-infarct cardiac function in the ISHR model. These functions may be involved in the inhibition of inflammation and the ventricular remodeling process and in the amelioration of glucose metabolism and endothelial dysfunction.
    International Journal of Molecular Sciences 02/2013; 14(2):2684-706. DOI:10.3390/ijms14022684 · 2.34 Impact Factor