Skip to main content
Article thumbnail
Location of Repository

Effects of statins on the secretion of human serum albumin in cultured HepG2 cells

By Chung-Eun Ha, Ji-Sook Ha, Andre G Theriault and Nadhipuram V Bhagavan


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

Topics: Research
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (1999). Adeli K: Effects of gamma-tocotrienol on ApoB synthesis, degradation, and secretion in HepG2 cells. Arterioscler Thromb Vasc Biol
    2. (2000). Assessment of serum albumin concentration as a risk factor for stroke and coronary disease in African Americans and whites.
    3. (1997). Association of serum albumin and mortality risk.
    4. (2003). Bhagavan NV: Human serum albumin and its structural variants mediate cholesterol efflux from cultured endothelial cells. Biochim Biophys Acta
    5. (1990). Brown MS: Regulation of the mevalonate pathway. Nature
    6. (2000). Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. Embo J
    7. (1992). Edelstein SL: Albumin levels as a predictor of mortality in the healthy elderly.
    8. (2001). Fahrenholz F: Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Natl Acad Sci USA
    9. (2001). Guralnik JM: The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol.
    10. (1995). Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation
    11. (2002). Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin. Circulation
    12. (2000). Involvement of oxysterols and lysophosphatidylcholine in the oxidized LDL-induced impairment of serum albumin synthesis by HEPG2 cells. Arterioscler Thromb Vasc Biol
    13. (1994). Isom HC: Suppression of albumin enhancer activity by Hras and AP-1 in hepatocyte cell lines. Mol Cell Biol
    14. (1996). Jr: All about albumin: Biochemsitry, Genetics, and Medical Applications. Volume 1.
    15. (2004). Kozawa O: Simvastatin enhances the regeneration of endothelial cells via VEGF secretion in injured arteries.
    16. (2005). Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol
    17. (2001). Liao JK: Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol
    18. (1994). Makuc DM: Relation between serum albumin concentration and stroke incidence and death: the NHANES I Epidemiologic Follow-up Study.
    19. (2004). Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators: Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
    20. (2003). RA: Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials. BMC Fam Pract
    21. (2000). Ridker PM: Are statins anti-inflammatory? Curr Control Trials Cardiovasc med
    22. (1998). Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. Jama
    23. (1991). RP: The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial.
    24. (2000). Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.
    25. (2002). Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes. Atherosclerosis
    26. (1986). Skalkeas G: Evidence for the existence of non-esterified cholesterol carried by albumin in rat serum. Atherosclerosis
    27. (2003). SL: Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. Jama
    28. (2003). SL: Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation
    29. (2003). Statin inhibition of HMG-CoA reductase: a 3-dimensional view. Atheroscler Suppl
    30. (2001). Statins and the acute-phase response.
    31. (2003). Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation. Endocrinology
    32. (2002). Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1. J Pharmacol Exp Ther
    33. (2000). The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med
    34. (2000). The structure of the catalytic portion of human HMG-CoA reductase. Biochim Biophys Acta
    35. (2005). Treating to New Targets (TNT) Investigators: Intensive lipid lowering with atorvastatin in patients with stable coronary disease.
    36. (1986). VG: Characterization of lipoproteins produced by the human liver cell line, Hep G2, under defined conditions.
    37. (1989). Whincup PH: Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.