Simvastatin inhibits tissue factor and plasminogen activator inhibitor-1 expression of glomerular mesangial cells in hypercholesterolemic rabbits.
Tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) activity and/or expression are upregulated in hypercholesterolemia. Despite extensive research on anti-thrombotic effect of statins, little is known about their effects on TF and PAI-1 expression in glomerular mesangial cells under hypercholesterolemic condition. Male rabbits were fed on either normal or high-cholesterol diet for 8 weeks. Then cholesterol-fed rabbits were randomly assigned to simvastatin or starch. At the end of 12 weeks, glomerular mesangial cells were collected. The concentrations of TF and PAI-1 mRNA were detected by RT-PCR. The plasma activities of TF and PAI-1 were determined with enzyme linked immunosorbent assay (ELISA) and chromogenic substrate method, respectively. The atherogenic diet caused a consistent increase in serum concentrations of total cholesterol (TC) and serum triglyceride (TG) (p < 0.05), increased TF and PAI-1 mRNA expression in glomerular mesangial cells and plasma activities as compared to the normal diet (p < 0.01). Four-week simvastatin treatment resulted in significant decrease of mesangial TF and PAI-1 mRNA (p < 0.01), and also of the plasma activities of TF (p < 0.05) and PAI-1 (p < 0.01). These results suggest that simvastatin might protect kidney from the formation of microthrombus under hypercholesterolemic condition and might be a possible pathogenesis of obesity-related glomerulopathy.
Wei
Jiali
J
Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Ma
Chunyang
C
Wang
Xiaomeng
X
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019821:Simvastatin / Q000494:pharmacology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000214:Acyl Coenzyme A; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D013925:Thromboplastin; D002784:Cholesterol; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases