LACK OF EFFECT OF LOVASTATIN THERAPY ON THE PARAMETERS OF WHOLE-BODY CHOLESTEROL-METABOLISM
LACK OF EFFECT OF LOVASTATIN THERAPY ON THE PARAMETERS OF WHOLE-BODY CHOLESTEROL-METABOLISM
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DOI：
10.1172/jci114777
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发表时间：
1990-09-01
影响因子：
15.9
通讯作者：
GOODMAN, DS
中科院分区：
文献类型：
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作者：
GOLDBERG, IJ;HOLLERAN, S;GOODMAN, DS
在9例高胆固醇血症患者中探讨了洛伐他汀治疗对机体胆固醇代谢参数的影响。在治疗前进行长期胆固醇转换研究，并在洛伐他汀治疗（40 mg/d）15个月后重复研究，同时继续治疗。讨论的主要问题是，洛伐他汀降低血浆胆固醇水平是否与全身胆固醇产生率降低或与胆固醇周转三池模型确定的可交换体内胆固醇池的大小相关。平均血浆胆固醇水平下降19.4%（从294至237 mg/dl），低密度脂蛋白胆固醇下降23.8%（从210至159 mg/dl）与洛伐他汀治疗。高密度脂蛋白胆固醇水平变化不显著。胆固醇生成率在治疗过程中没有显著变化（1.09 ± 0.05）。0.10[平均值+-。S. D.]对比1.17 .+-。0.09 g/d）。相比之下，考来替泊和烟酸治疗在其他三个科目增加了一倍以上的胆固醇生产率（1.14。0.28与2.42 .+-相比。0.34 g/d）。因此，羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制洛伐他汀在这里使用的治疗剂量没有改变全身胆固醇合成的稳态。尽管血浆胆固醇水平发生了变化，但M1、M3或Mtot值、快速、缓慢和全身可交换胆固醇池的大小均未发生显著变化。结论：用于降低血浆胆固醇的洛伐他汀疗法不会导致体内胆固醇库的相应减少或全身胆固醇合成速率的降低。在长期洛伐他汀治疗期间存在的新稳态中，沿着HMG-CoA还原酶和LDL受体基因表达的增加，身体补偿药物的作用，使得胆固醇产生速率和组织池大小与治疗前值相比没有改变。
The effects of lovastatin therapy on the parameters of body cholesterol metabolism were explored in nine hypercholesterolemic patients. Long-term cholesterol turnover studies were performed before therapy, and were repeated after 15 mo of lovastatin therapy (40 mg/d) while continuing on therapy. The major question addressed was whether a reduction in plasma cholesterol level with lovastatin would be associated with a reduction in the whole-body production rate of cholesterol or with the sizes of exchangeable body cholesterol pools as determined by the three-pool model of cholesterol turnover. The mean plasma cholesterol level decreased 19.4% (from 294 to 237 mg/dl), and low-density lipoprotein cholesterol decreased 23.8% (from 210 to 159 mg/dl) with lovastatin therapy. Changes in high-density lipoprotein cholesterol level were not significant. The cholesterol production rate did not change significantly with therapy (1.09 .+-. 0.10 [mean .+-. S.D.] vs. 1.17 .+-. 0.09 g/d). By comparison, colestipol and niacin treatment in three other subjects more than doubled the cholesterol production rate (1.14 .+-. 0.28 vs. 2.42 .+-. 0.34 g/d). Thus, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibition by lovastatin at the therapeutic dose used here did not change the steady-state of whole-body cholesterol synthesis. Despite the changes in plasma cholesterol levels, no significant changes were seen in the values of M1, of M3 or of Mtot, the sizes of the pools of rapidly, of slowly, and of total body exchangeable cholesterol. Conclusion: lovastatin therapy to lower plasma cholesterol does not lead to corresponding reductions in body cholesterol pools or to a reduction in the rate of whole-body cholesterol synthesis. In the new steady state that exists during long-term lovastatin therapy, along with increased expression of the genes for HMG-CoA reductase and the LDL receptor, the body compensates for the effects of the drug so that cholesterol production rate and tissue pool sizes are not changed from pretreatment values.