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Research Article

Homocysteine Promotes Vascular Smooth Muscle Cell Migration by Induction of the Adipokine Resistin

¹Peking University ²King's College London, UK

Submitted 13 July 2009 ; revised 11 September 2009 ; accepted in final form 14 September 2009

Adipokines may represent a mechanism linking insulin resistance to cardiovascular disease. We have previously shown that homocysteine (Hcy), an independent risk factor for cardiovascular disease, can induce the expression and secretion of resistin, a novel adipokine, in vivo and in vitro. Since vascular smooth muscle cell (VSMC) migration is a key event in vascular disease, we hypothesized that adipocyte-derived resistin is involved in Hcy-induced VSMC migration. To confirm our hypothesis, Sprague-Dawley rat aortic SMCs were co-cultured with Hcy-stimulated primary rat epididymal adipocytes or treated directly with increasing concentrations of resistin for up to 24 h. Migration of VSMCs was investigated. Cytoskeletal structure and cytoskeleton-related proteins were also detected. The results showed that Hcy (300-500 µM) increased migration significantly in VSMCs co-cultured with adipocytes but not in VSMC culture alone. Resistin alone also significantly increased VSMC migration in a time- and concentration-dependent manner. Resistin siRNA significantly attenuated the VSMC migration in the co-culture system, which indicated that adipocyte-derived resistin mediates Hcy-induced VSMC migration. On cell spreading assay, resistin induced the formation of focal adhesions near the plasma membrane, which suggests cytoskeletal rearrangement via an integrin 5β1-focal adhesion kinase/paxillin-Rac1 pathway. Our data demonstrate that Hcy promotes VSMC migration through a paracrine or endocrine effect of adipocyte-derived resistin, which provides further evidence of the adipose-vascular interaction in metabolic disorders. The migratory action exerted by resistin on VSMCs may account in part for the increased incidence of restenosis in diabetic patients.

Homocysteine; Vascular smooth muscle cells (VSMCs); Migration; Resistin