Effects Of Pioglitazone On The Proliferation Of Vascular Smooth Muscle Cells In Rabbits With Atherosclerosis

Objectives: To investigate the effects of pioglitazone(pio) on the proliferation of vascular smooth muscle cells (VSMCs) in Rabbits with Atherosclerosis(AS)Methods:Forty male New Zealand white rabbits were randomly divided into 5 groups:A,normal control group treated with normal sodium,B,normal group treated with low dosage pio(2.5mg/kg.d),C,pathological control group treated with normal sodium,D,pathological group treated with low dosage pio(2.5mg/ kg.d), E,pathological group treated with high dosage pio(10mg/ kg.d). Rabbits in groups A and B were fed with normal chow ,Rabbits in groups B,C and D were fed with high fat diet.After 2 weeks,the surgery of abdominal aorta endothelium denudation was managed in the last three groups .All rabbits were continued on their respective dietary and treated with two dosage of pio for eight weeks. all rabbits were sacrificed at the end of the 10th week Blood glucose and serum lipids levels were measured on the 0,10th weeks. Aortae were analyzed by histopathological examination. The protein expression of peroxisome proliferator-activated receptor gamma(PPARγ),platelet-derived growth factor-B (PDGF—B),proliferating cell nuclear antigen(PCNA) andα-smooth muscle actin(α-SMA)was detected by immunohistochemistry .The mRNA expression of PPARγand PDGF—B was examined by reverse transcription-polymerase chain reaction(RT-PCR). Results: (1) Dislipidemia was successfully reproduced in rabbits after 10 weeks. Administration of pioglitazone significantly could greatly decreased serum TG and greatly increased HDL-C in dose-dependent way (P<0.01),but TC and LDL-C were not significantly decreased(P>0.05).The differences of blood glucose between 0 week and 10th weeks were not significant(P>0.05).(2) The atherosclerosis model with rabbits had been successfully established with high fat diet and abdominal aorta endothelium denudation. There were severe pathological lesions in group C. Pioglitazone can inhibit the development of atherosclerosis, the pathological of atherosclerosis in group D and group E was significantly milder than group C (P<0.01). Pioglitazone could greatly diminish the area of plaque and thickness of endomembrane in dose-dependent way.(3) The expression of PPARγmRNA and protein greatly increased in group C when comparing to group A (P<0.01). The expression of PPARγin group D and group E was lower (P<0.01) than in group C and higher than in group A (P<0.01).(4) Compared with group A,the mRNA and protein expression of PPARγincreased significantly (P<0.01);the protein expression of PCNA also increased significantly (P<0.01).Compared with group C, they were significantly reduced in group D and group E(dose dependent) (P<0.01),but still higher than in group A. (P<0.01)(5)The protein expression ofα-SMA in group C was significantly decreased when compared to group A (P<0.01). Administration of pioglitazone can significantly increased the protein expression ofα-SMA. In group D and group E, they were greatly higher than in group C (P<0.01).(6)The expression of PCNA was positively correlated with the expression of PDGF-B﹙r=0.914, p<0.01).The expression ofα-SMA was negatively correlated with the expression of PDGF-B (r=-0.858,p<0.01﹚.Conclusion:Pioglitazone can activate PPARγ, and then decrease serum TG,increase HDL-C, inhibit the expression of PDGF—B , decrease the expression of PCNA, increase the expression ofα-SMA . These may be contribute to the inhibition of the proliferation of vascular smooth muscle cells and anti-atherosclerosis in Rabbits with AS.