The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype.
The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype.
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DOI：
10.1016/j.bbalip.2011.09.008
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Deeb SS
中科院分区：
文献类型：
--
作者：
Brunzell JD;Zambon A;Deeb SS
肝脂酶（HL）活性升高或降低与冠状动脉疾病（CAD）相关。这与在一些人群研究中影响HL活性的基因变异与CAD风险增加相关，而在其他人群研究中则不相关的发现一致。在这篇综述中，我们将解释影响HL对CAD的影响的条件。HL增加与更小和更致密的LDL（sdLDL）和HDL（HDL 3）颗粒相关，而HL减少与更大和更有浮力的LDL和HDL颗粒相关。HL活性对CAD风险的影响取决于基础脂蛋白表型或疾病。中心性肥胖伴高脂血症（HTG）与高HL活性相关，高HL活性导致形成致动脉粥样硬化的sdLDL。在没有HTG的情况下，其中富含胆固醇酯的大浮力LDL是突出的，HL升高不会增加CAD的风险。在HTG患者中，降低HL活性的药物治疗选择性地减少sdLDL颗粒，这是一种抗动脉粥样硬化作用。升高HDL 2胆固醇的药物治疗并没有降低CAD的风险。在发生胆固醇酯转移蛋白（CETP）或HL抑制的试验中，HDL 2升高最有可能是由于HDL 2催化剂的抑制和胆固醇逆向转运（RCT）受损。在单纯性高胆固醇血症但甘油三酯水平正常且LDL颗粒较大的患者中，HL活性增加是有益的;可能是因为它增加了RCT。降低HL活性的药物可能仅通过选择性清除血浆中的sdLDL颗粒来降低sdLDL高脂血症患者的CAD风险，这将覆盖RCT的潜在促动脉粥样硬化效应。
Increased or decreased hepatic lipase (HL) activity has been associated with coronary artery disease (CAD). This is consistent with the findings that gene variants that influence HL activity were associated with increased CAD risk in some population studies but not in others. In this review, we will explain the conditions that influence the effects of HL on CAD. Increased HL is associated with smaller and denser LDL (sdLDL) and HDL (HDL3) particles, while decreased HL is associated with larger and more buoyant LDL and HDL particles. The effect of HL activity on CAD risk is dependent on the underlying lipoprotein phenotype or disorder. Central obesity with hypertriglyceridemia (HTG) is associated with high HL activity that leads to the formation of sdLDL that is proatherogenic. In the absence of HTG, where large buoyant cholesteryl ester-enriched LDL is prominent, elevation of HL does not raise the risk for CAD. In HTG patients, drug therapy that decreases HL activity selectively decreases sdLDL particles, an antiatherogenic effect. Drug therapy that raises HDL2 cholesterol has not decreased the risk for CAD. In trials where inhibition of cholesterol ester transfer protein (CETP) or HL occurs, the increase in HDL2 most likely is due to inhibition of catabolism of HDL2 and impairment of reverse cholesterol transport (RCT). In patients with isolated hypercholesterolemia, but with normal triglyceride levels and big-buoyant LDL particles, an increase in HL activity is beneficial; possibly because it increases RCT. Drugs that lower HL activity might decrease the risk for CAD only in hypertriglyceridemic patients with sdLDL by selectively clearing sdLDL particles from plasma, which would override the potentially pro-atherogenic effect on RCT.
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冠状动脉疾病的新遗传基因座的大规模关联分析。
DOI：
10.1161/atvbaha.108.181388
发表时间：
2009-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Coronary Artery Disease Consortium;Samani NJ;Deloukas P;Erdmann J;Hengstenberg C;Kuulasmaa K;McGinnis R;Schunkert H;Soranzo N;Thompson J;Tiret L;Ziegler A
通讯作者：
Ziegler A
影响因子：
16.2
作者：
Carr, MC;Knopp, RH;Anderson, PW
通讯作者：
Anderson, PW
影响因子：
15.9
作者：
Edmondson, Andrew C.;Brown, Robert J.;Rader, Daniel J.
通讯作者：
Rader, Daniel J.
影响因子：
158.5
作者：
Barter, Philip J.;Caulfield, Mark;Brewer, Bryan
通讯作者：
Brewer, Bryan
DOI：
10.1136/bmj.b92
发表时间：
2009-02-16
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Briel M;Ferreira-Gonzalez I;You JJ;Karanicolas PJ;Akl EA;Wu P;Blechacz B;Bassler D;Wei X;Sharman A;Whitt I;Alves da Silva S;Khalid Z;Nordmann AJ;Zhou Q;Walter SD;Vale N;Bhatnagar N;O'Regan C;Mills EJ;Bucher HC;Montori VM;Guyatt GH
通讯作者：
Guyatt GH