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 arresting the development of arterial restenosis after angioplasty.


METHODS
De-endothelialization injury of rabbit aortae, common iliac and femoral arteries using balloon angioplasty and the expression of growth factors such as platelet derived growth factor-B (PDGF-B), transforming growth factor beta-1 (TGF beta-1), and fibroblast growth factors (bFGF) were investigated. Total serum cholesterol (TC) and triglycerides (TG) were analyzed during and after the treatment using either simvastatin combined with gemfibrozil or simvastatin alone for 6 weeks.


RESULTS
Serum total cholesterol and triglycerides were only slightly to moderately 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/medial ratio (r = 0.5873, P < 0.05). PDGF-B detected by immuno-histochemistry and RT-PCR analysis showed that the release of PDGF-B was inhibited by simvastatin and gemfibrozil after de-endothelialization. RT-PCR analysis showed that TGF beta-1 was increased in the neointima in two treatment groups but 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 treatment.


CONCLUSIONS
In addition to the lipid lowering effect, both simvastatin and gemfibrozil also influence the release of PDGF-Band TGF-1 in the neointima after de-endothelialization.
Zhou
Y
Y
Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
Liu
X
X
She
M
M
D000818:Animals; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000293:injuries*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015248:Gemfibrozil / Q000494:pharmacology; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D006133:Growth Substances; D000960:Hypolipidemic Agents; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014280:Triglycerides; D016222:Fibroblast Growth Factor 2; D002784:Cholesterol; D019821:Simvastatin; D015248:Gemfibrozil