Experimental Research On The Inhibition By HO-1 And Rapamycin In The Phenotypic Modulation In Rat VSMCs Induced By PDGF

Background: There is a common pathophysiology perspective in many cardiovascular disease such as vein graft, restenosis after revascularization and atherosclerosis. The VSMCs generated from tunica media vasorum got the ability to infiltrate and proliferate in the endangium what called vascular phenotypic modulation. PDGF is a major kind of mitogen which could promote the modulation and proliferation of VSMCs. Heme oxygenase is the enzyme in heme breakdown to generate carbon monoxide, biliverdin, and free ferrous iron, which play a crucial role in the protection of the body. Many research suggested that HO-1 could inhibit the proliferation of VSMCs. Rapamycin, considered an effective immunosuppressant devoid of chronic toxicity, is shown to exhibit deleterious effects on the viability and function of cells in a number of cell types including VSMCs. The sirolimus-eluting stent (SES) has emerged as a promising therapy to prevent restenosis. So we designed this study to observe the inhibition by HO-1 and rapamycin of the phenotypic modulation in rat VSMCs induced by PDGF in vitro.Objective: To observe the inhibition by HO-1 and rapamycin of the phenotypic modulation in rat VSMCs induced by PDGF in vitro, to observe the inhibition by HO-1 and rapamycin of the phenotypic modulation in rat VSMCs induced by PDGF in vitro.Methods: Primary rat aorta vascular smooth muscle cells were isolated andcultured. The PDGF-BB to promote the phenotypic modulate of VSMCs. Hemin with different dose and rapamycin were added respectively. And SM-a-actin and PCNA were analysed with immunofluorescencestaining and Confocal laser scaning microscope respectively.Results: The SM-a-actin was down-regulation and the PCNA was up-regulation in VSMCs treat with PDGF-BB. Co-culture the VSMCs with PDGF-BB and either hemin or rapamycin could retroconversion the effect. High dose of hemin represent the more powerful ability to prevent the phenotypic modulation of VSMCs.Conclusion: 1.PDGF-BB could prevent the phenotypic modulation in primary rat VSMCs. 2. Partial VSMCs differentiated phenotype exist in vivo possibly and may got dedifferentiation idiopathic in vitro. 3.Ho-1 induced by hemin could retroconversion the effect of PDGF-BB induced phenotypic modulation in dose dependent manner. 4. Rapamycin could retroconversion the effect of PDGF-BB induced phenotypic modulation in low dose.