Ha Chung-Eun, Ha Ji-Sook, Theriault Andre G, Bhagavan Nadhipuram V
Department of Native Hawaiian Health, John A, Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI 96813, USA.
J Biomed Sci. 2009 Mar 16;16(1):32. doi: 10.1186/1423-0127-16-32.
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.
他汀类药物通过抑制HMG - CoA还原酶来减少胆固醇生物合成，从而降低血清中的总胆固醇和低密度脂蛋白胆固醇水平，进而降低心血管疾病（CVD）的发病率。他汀类药物还已知可通过抑制胆固醇合成中的下游中间体来调节各种细胞功能，如基因表达、细胞增殖和程序性细胞死亡。在本研究中，我们研究了他汀类药物对培养的HepG2细胞分泌血清白蛋白的可能影响，因为高水平的血清白蛋白与降低CVD风险相关，并且他汀类药物除了对血清总胆固醇和低密度脂蛋白胆固醇水平有影响（即多效性作用）外，还通过其他作用有效降低CVD风险。我们的结果表明，与对照组相比，辛伐他汀使HSA分泌增加了32.3%。在我们测试的3种他汀类类似物中，与对照组相比，辛伐他汀对HSA分泌表现出最高的刺激作用。我们的研究还表明，辛伐他汀处理使HepG2细胞中HSA分泌增加是由于HSA合成速率增加，而不是由于HSA翻译后降解速率降低。我们的发现表明他汀类药物治疗通过刺激HSA生物合成在预防CVD方面还有另一个额外益处。
