The pathophysiology of excess plasma-free cholesterol.
The pathophysiology of excess plasma-free cholesterol.
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DOI：
10.1097/mol.0000000000000899
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发表时间：
2023-12-01
影响因子：
4.4
通讯作者：
Pownall, Henry J.
中科院分区：
文献类型：
--
作者：
Gillard, Baiba K.;Rosales, Corina;Gotto Jr, Antonio M.;Pownall, Henry J.
几项大型研究表明，全因和动脉粥样硬化性心血管疾病导致的死亡率增加。在大多数临床环境中，血浆高密度脂蛋白胆固醇被确定为游离胆固醇和胆固醇酯的总和，这两种分子具有截然不同的代谢路线。我们研究了支持血浆hdl -胆固醇升高的病理效应是由于HDL-C的游离胆固醇成分的高水平引起的这一概念的证据。在一小部分人群中，高血浆高密度脂蛋白胆固醇与死亡率增加有关。在高密度脂蛋白受体缺陷小鼠（Scarb1-/-）（一种高密度脂蛋白c升高的临床前模型）中进行的类似观察表明，这些患者中高密度脂蛋白的病理成分是血浆高密度脂蛋白fc升高。对人类和小鼠数据的综合考虑表明，临床试验，特别是在高血浆高密度脂蛋白的情况下，应该测量游离胆固醇和胆固醇酯，而不仅仅是总胆固醇。
Several large studies have shown increased mortality due to all-causes and to atherosclerotic cardiovascular disease. In most clinical settings, plasma HDL-cholesterol is determined as a sum of free cholesterol and cholesteryl ester, two molecules with vastly different metabolic itineraries. We examine the evidence supporting the concept that the pathological effects of elevations of plasma HDL-cholesterol are due to high levels of the free cholesterol component of HDL-C. In a small population of humans, a high plasma HDL-cholesterol is associated with increased mortality. Similar observations in the HDL-receptor deficient mouse (Scarb1-/-), a preclinical model of elevated HDL-C, suggests that the pathological component of HDL in these patients is an elevated plasma HDL-FC. Collective consideration of the human and mouse data suggests that clinical trials, especially in the setting of high plasma HDL, should measure free cholesterol and cholesteryl esters and not just total cholesterol.
影响因子：
6.5
作者：
Rosales, Corina;Yelamanchili, Dedipya;Gillard, Baiba K.;Liu, Jing;Gotto Jr, Antonio M.;Pownall, Henry J.
通讯作者：
Pownall, Henry J.