Effects Of Fluvastatin And Sodium Ferulate On Attachment And Migration Of Vascular Smooth Muscle Cells

Objective: To investigate the effects of fluvastatin (Flu) and sodium ferulate (SF) onattachment and migration of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR).Methods: Cultured VSMCs derived from the aorta of 8-week-old SHR were used.Attachment of VSMCs was conducted using flat-bottomed 96-well polystyrene plates. Modified Boyden chamber technique was employed for VSMCs migration accessment. The concentration of intracellular free calcium ion ([Ca2+]i) was measured with fluorescent Ca2+ indicator- fura-2/AM.Results: 1. Both fibronectin (FN) and fibrinogen (Fg) induced the attachment ofVSMCs in dose- and time-dependent manner, which was significantly inhibited by Flu (10-9~ 10-5mol/L) and SF (10-7~ 10-3mol/L) . The inhibitory effects of Flu on attachment in VSMCs induced by FN and Fg were significant, and maximal inhibitory rates were 70.29% and 78.38% with 10-5Mol/L Flu (P<0. 01). Attachment of VSMCs stimulated by FN and Fg was remarkably suppressed by SF in a range of 10-6~10-3mol/L, with maximal inhibition rate at 67.12% and 70.23% (P<0. 01).2. Both FN and Fg dose-dependently promoted migration of VSMCs. The effective concentration fell on 40-60 g/ml and l~5mg/ml. The migration of VSMCs in response to FN and Fg was suppressed by Flu in a concentration-dependent manner, with maximal inhibition rate at 69.79% and 87.06%(P<0. 01). The maximal inhibition rate of SF on the migration of VSMCs induced by FN and Fg was at 67.01% and 81.19% respectively (P<0. 01). Both platelet derived growth factor-BB (PDGF-BB) and endothelin-1 (ET-1) significantly invoked the migration of VSMCs, with a peak response at 10ng/ml and10-7Mol/L respectively, which was suppressed by pre-treatment with Flu and SF in a dose-dependent manner, with a peak inhibitory rate at 85.44%, 94.87% (Flu) and 91.92%, 95.79% ( SF ) respectively (P<0. 01).3. FN, Fg, PDGF-BB and ET-1 all provoked the rise of [Ca2+]i in VSMCs from SHR, and the increase of [Ca2+]i in response to these reagents were 53.93±8.71nM (FN), 94.90 ± 37.63nM (Fg), 112.38 ± 23.85nM (PDGF-BB), 95.26 ±35.93 nM (ET-1). The peak responses of [Ca2+]i fell on the concentration of PDGF 10ng/ml and ET-1 10-8Mol/L respectively. The elevation of [Ca2+]i in VSMCs stimulated by FN, Fg, PDGF-BB and ET-1 was significantly suppressed by Flu and SF.Conclusions:1. FN and Fg promote the adhesion and migration of VSMCs from SHR.2. PDGF-BB and ET-1 induce the migration of VSMCs.3. Flu and SF inhibite the attachment and migration of VSMCs induced by FN, Fg, PDGF-BB and ET-1 in dose-dependent manner.4. FN, Fg, PDGF-BB and ET-1 all provoke the rise of [Ca2+]i in VSMCs5. Flu and SF inhibite the rise of [Ca2+]i in VSMCs induced by FN, Fg, PDGF-BB and ET-1.