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首页> 外文期刊>Circulation journal >ANGPTL3 Inhibitors - Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism -
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ANGPTL3 Inhibitors - Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism -

机译:Angptl3抑制剂 - 通过调控脂质代谢的调控作用于心血管疾病 -

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摘要

Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. The regulation of plasma lipid levels by ANGPTL3 is controlled via affecting lipoprotein lipase and endothelial lipase-mediated hydrolysis of triglycerides (TGs) and phospholipids. ANGPTL 3, along with the other 2 members, 4 and 8, is a key to balancing the distribution of circulating TGs between white adipose tissue (WAT) and oxidative tissues. Thus, ongoing trials with newly discovered medications in the form of monoclonal antibodies or antisense oligonucleotides with novel targets are under analysis and may represent a fresh frontier in the treatment of hyperlipidemia and CAD.
机译:升高的血浆脂质水平与动脉粥样硬化有关,冠状动脉疾病(CAD)的标志,由动物研究记录以及血管造影和临床研究。通过生活方式改变治疗高脂血症和降脂剂的能力与动脉粥样硬化的缓慢进展和主要冠状动脉事件的发病率降低有关。血管发成素样蛋白(Angptls)是一种在肝脏中表达的分泌糖蛋白的一系列分泌的糖蛋白,其与血管生成血管生成的主要调节剂共享常见的结构域特征。虽然安普粉刺不能与内皮细胞表达的血管发成素受体结合,但2个Angptl家族成员(Angptl3和Angptl4)具有临床重要性,因为它们对小鼠和人类的脂蛋白代谢的明确效果。通过影响脂蛋白脂肪酶和内皮脂肪酶介导的甘油三酯(TGS)和磷脂的水解来控制通过Angptl3的血浆脂质水平的调节。 Angptl 3以及其他2个构件4和8是平衡白色脂肪组织(Wat)和氧化组织之间循环Tgs分布的关键。因此,正在进行与新发现单克隆抗体或反义寡核苷酸形式的新发现的试验,其具有新的靶标在分析中,并且可以在治疗高脂血症和CAD的治疗中代表新的前沿。

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