Molecular basis for the effect of lipid lowering drugs on growth factors after de-endothelialization

Objective To study the mechanism and effect of lipid lowering drugs in arre sting the development of arterial restenosis after angioplasty. Methods De-endothelialization injury of rabbit aortae, common iliac and fem oral arteries using balloon angioplasty and the expression of growth factor s such as platelet derived growth factor-B (PDGF-B), transforming growth fa ctor beta -1 (TGF beta -1), and fibroblast growth factos (bFGF) were invest igated. Total serum cholesterol (TC) and triglycerides (TG) were analyzed d uring and after the treatment using either simvastatin combined with gemfib rozil or simvastatin alone for 6 weeks. Results Serum total cholesterol and triglycerides were only slightly to mod erately increased after high cholesterol ration intake lasting for 6 weeks in rabbits of two therapeutic groups (simvastatin plus gemfibrozil or only simvastatin). A positive correlation was found between TC and intimal/media l ratio ( r = 0.5873, P < 0.05). PDGF-B detected by immuno-histochemistry a nd RT-PCR analysis showed that the release of PDGF-13 was inhibited by simv astatin and gemfibrozil after de-endothelialization. RT-PCR analysis showed that TGF beta -1 was increased in the neointima in two treatment groups bu t no definite change was seen in the mRNA of bFGF in the smooth muscle cell (SMC) of the balloon-injured arteries even under lipid lowering drug treat ment. Conclusion In addition to the lipid lowering effect, both simvastatin and g emfibrozil also influence the release of PDGF-Band TGF-1 in the neointima a fter de-endothelialization.