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首页> 外文期刊>Current opinion in lipidology >Lysosomal acid lipase and atherosclerosis.
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Lysosomal acid lipase and atherosclerosis.

机译：溶酶体酸性脂肪酶和动脉粥样硬化。

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PURPOSE OF REVIEW: Atherosclerosis remains the leading cause of death in the developed countries. In addition to lipid-lowering drugs - statins, dietary control, and exercise, new approaches are needed for the treatment and prevention of atherosclerosis. This review will focus on the role(s) of lysosomal acid lipase and its use as an enzyme therapy to reduce atherosclerotic lesions in a mouse model and to examine the molecular basis supporting this novel strategy and its mechanism of effect. RECENT FINDINGS: Administration of human lysosomal acid lipase via tail vein into mice with atherosclerosis eliminates early aortic and coronary ostial lesions and reduces lesional size in advanced disease. The reduction of advanced lesional area is related to decreases in foamy macrophages, collagen positive areas, and necrotic areas. Compared with sham-treated mice, the human lysosomal acid lipase-treated mice also have reduced levels of plasma cholesteryl esters, and reduced levels of hepatic cholesterol and triglycerides. SUMMARY: These studies indicate that administrated lysosomal acid lipase affects the atherogenesis by at least two mechanisms: (1) direct targeting of lesional macrophages with resultant decreases in cholesteryl esters and triglyceride in the lysosomes of macrophages in the lesions; (2) systemic effects that mediate the liver to reduce the hepatic cholesteryl ester and triglyceride release, possibly leading to reduced production of VLDL and LDL.
机译：审查目的：动脉粥样硬化仍然是发达国家的主要死亡原因。除了降脂药物-他汀类药物，饮食控制和运动外，还需要新的方法来治疗和预防动脉粥样硬化。这项审查将侧重于溶酶体酸性脂肪酶的作用及其在减少小鼠模型中动脉粥样硬化病变的酶疗法中的应用，并研究支持这种新策略的分子基础及其作用机理。最新发现：通过尾静脉将人溶酶体酸性脂肪酶给予患有动脉粥样硬化的小鼠，可消除早期主动脉和冠状动脉病变，并减少晚期疾病的病变大小。晚期病变区域的减少与泡沫巨噬细胞，胶原蛋白阳性区域和坏死区域的减少有关。与假治疗的小鼠相比，溶酶体酸性脂肪酶治疗的小鼠血浆胆固醇酯水平降低，肝胆固醇和甘油三酸酯水平降低。概述：这些研究表明，溶酶体酸性脂肪酶的给药至少通过两种机制影响动脉粥样硬化的形成：（1）直接靶向病变巨噬细胞，导致病变中巨噬细胞溶酶体中的胆固醇酯和甘油三酸酯减少; （2）介导肝脏减少肝胆固醇酯和甘油三酸酯释放的全身作用，可能导致VLDL和LDL的产生减少。

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