Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ - 30/04/18
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Graphical abstract |
Highlights |
• | Nesfatin-1 promoted VSMC phenotype switch from contractile to synthetic state. |
• | Nesfatin-1 stimulated VSMC proliferation and migration. |
• | MMP2/MMP-9 and PPARγ participated in the action of nesfatin-1. |
• | Knockdown of nesfatin-1 ameliorated neointima formation after carotid injury. |
Abstract |
The dedifferentiation, proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the progression of hypertension, atherosclerosis and intimal hyperplasia. Nesfatin-1 is a potential modulator in cardiovascular functions. However, the role of nesfatin-1 in VSMC biology has not been explored. The present study was designed to determine the regulatory role of nesfatin-1 in VSMC proliferation, migration and intimal hyperplasia after vascular injury. Herein, we demonstrated that nesfatin-1 promoted VSMC phenotype switch from a contractile to a synthetic state, stimulated VSMC proliferation and migration in vitro. At the molecular level, nesfatin-1 upregulated the protein and mRNA levels, as well as the promoter activities of matrix metalloproteinase 2 (MMP-2) and MMP-9, but downregulated peroxisome proliferator-activated receptor γ (PPARγ) levels and promoter activity in VSMCs. Blockade of MMP-2/9 or activation of PPARγ prevented the nesfatin-1-induced VSMC proliferation and migration. In vivo, knockdown of nesfatin-1 ameliorated neointima formation following rat carotid injury. Taken together, our results indicated that nesfatin-1 stimulated VSMC proliferation, migration and neointimal hyperplasia by elevating MMP2/MMP-9 levels and inhibiting PPARγ gene expression.
Le texte complet de cet article est disponible en PDF.Keywords : Vascular smooth muscle cells, Proliferation, Migration, Phenotype, Matrix metalloproteinase
Plan
Vol 102
P. 711-717 - juin 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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