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Home > Medical Professionals > Research Initiatives Conference > Poster Abstracts Accepted > Rzucidlo Statins Induce Phenotypic Modulation

Statins Induce Phenotypic Modulation of Vascular Smooth Muscle Cells

Eva M Rzucidlo, Kathleen A Martin, Robert J Wagner, Richard A Powell, Richard J Powell
Dartmouth Hitchcock Medical Center, Lebanon, NH

INTRODUCTION: During vascular injury, smooth muscle cells (SMC) dedifferentiate from contractile to synthetic phenotype. Statins are potent inhibitors of cholesterol biosynthesis. They also have favorable effects on arterial wall remodeling that are independent of their cholesterol lowering effect. The hypothesis tested is statins promote differentiation of cultured human aortic SMC (HVSMC).
METHODS: HSMC were cultured alone or with Lovastatin (2ug/ml) for 24 hours. Proliferation was determined by incorporation of Brdu. Differentiated phenotype was determined by cell morphology, cell size, total collagen (extracellular matrix) production and contractile protein expression. Cell surface areas of HVSMC were measured by planimetry. Western blot analysis was performed using contractile protein antibodies to calponin and h-caldesmon antibody. Extracellular matrix (collagen) production was determined by incorporation of tritiated proline over 24 hours.
RESULTS: Lovastatin inhibited HVSMC proliferation by 67% (p=.04). HVSMC cultured alone assumed a de-differentiated phenotype as noted by cell morphology and cell area (3172± 197μ²m). Treatment with Lovastatin resulted in a significantly smaller cell surface area compared to cells cultured alone (1041 ± 44μ²m, p<.0001). Lovastatin decreased total collagen production by 30% (p<.01). Up-regulation of calponin and h-caldesmon protein was observed in SMC treated with Lovastatin and confirmed by Western blot . Figure 1 shows a representative Western blot of calponin concentration with and without Lovastatin.
CONCLUSION: Lovastatin treatment promoted differentiation of VSMC. This was associated with a decrease in proliferation and extracellular matrix synthesis. The effect of statins on SMC phenotype likely contributes to their beneficial effect on vascular wall remodeling.