Effects of statins on the secretion of human serum albumin in cultured HepG2 cells.
Statins reduce cholesterol biosynthesis by inhibiting HMG-CoA reductase and thereby lower total cholesterol and LDL cholesterol levels in serum, which in turn lower the incidence of cardiovascular disease (CVD). Statins are also known to modulate various cellular functions such as gene expression, cell proliferation, and programmed cell death through inhibition of downstream intermediates in cholesterol synthesis. In this study, we have investigated the possible effects of statins on the secretion of serum albumin from cultured HepG2 cells since high levels of serum albumin are associated with reduced risks for CVD and statins are effective in lowering the risk of CVD through other effects in addition to their effects on serum total cholesterol and LDL cholesterol levels, known as pleiotropic effects. Our results showed that simvastatin increased HSA secretion up to 32.3% compared to the control group. Among 3 statin analogs we tested, simvastatin exhibited the highest stimulatory effects on HSA secretion compared to the control group. Our study also showed that the increased HSA secretions from HepG2 cells by simvastatin treatments were due to the increased rate of HSA synthesis, not due to the reduced posttranslational degradation rate of HSA. Our finding suggests another added benefit of statins' treatments in preventing CVD through stimulation of HSA biosynthesis.
Ha
Chung-Eun
CE
Department of Native Hawaiian Health, John A, Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI 96813, USA. chungeun@hawaii.edu
Ha
Ji-Sook
JS
Theriault
Andre G
AG
Bhagavan
Nadhipuram V
NV
D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control; D002460:Cell Line / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012709:Serum Albumin; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin