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首页> 外文期刊>Cardiovascular drugs and therapy >Research Progress on the Involvement of ANGPTL4 and Loss-of-Function Variants in Lipid Metabolism and Coronary Heart Disease: Is the 'Prime Time' of ANGPTL4-Targeted Therapy for Coronary Heart Disease Approaching?
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Research Progress on the Involvement of ANGPTL4 and Loss-of-Function Variants in Lipid Metabolism and Coronary Heart Disease: Is the 'Prime Time' of ANGPTL4-Targeted Therapy for Coronary Heart Disease Approaching?

机译:脂质代谢和冠心病中Angptl4和函数丧失变体的参与的研究进展:是冠心病接近冠心病治疗的“黄金时期”?

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Background Multiple genetic studies have confirmed the definitive link among the loss-of-function variants of angiogenin-like protein 4 (ANGPTL4), significantly decreased plasma triglyceride (TG) levels, and reduced risk of coronary heart disease (CHD). The potential therapeutic effect of ANGPTL4 on dyslipidemia and CHD has been widely studied. Objective This review provides a detailed introduction to the research progress on the involvement of ANGPTL4 in lipid metabolism and atherosclerosis and evaluates the efficacy and safety of ANGPTL4 as a therapeutic target for CHD. Relevant Findings By inhibiting lipoprotein lipase (LPL) activity, ANGPTL4 plays a vital role in the regulation of lipid metabolism and energy balance. However, the role of ANGPTL4 in regulating lipid metabolism is tissue-specific. ANGPTL4 acts as a locally released LPL inhibitor in the heart, skeletal muscle and small intestine, while ANGPTL4 derived from liver and adipose tissue mainly acts as an endocrine factor that regulates systemic lipid metabolism. As a multifunctional protein, ANGPTL4 also inhibits the formation of foam cells in macrophages, exerting an anti-atherogenic role. The function of ANGPTL4 in endothelial cells is still uncertain. The safety of ANGPTL4 monoclonal antibodies requires further evaluation due to their potential adverse effects. Conclusion The biological characteristics of ANGPTL4 are much more complex than those demonstrated by genetic studies. Future studies must elucidate how to effectively reduce the risk of CHD while avoiding potential atherogenic effects and other complications before the "prime time" of ANGPTL4-targeted therapy arrives.
机译:背景:多项遗传学研究证实了血管生成素样蛋白4(ANGPTL4)功能丧失变体、血浆甘油三酯(TG)水平显著降低和冠心病(CHD)风险降低之间的明确联系。ANGPTL4对血脂异常和冠心病的潜在治疗作用已被广泛研究。目的详细介绍血管紧张素样肽4(ANGPTL4)参与脂质代谢和动脉粥样硬化的研究进展,并评价其作为冠心病治疗靶点的有效性和安全性。ANGPTL4通过抑制脂蛋白脂肪酶(LPL)活性,在调节脂质代谢和能量平衡中发挥重要作用。然而,ANGPTL4在调节脂质代谢中的作用是组织特异性的。ANGPTL4在心脏、骨骼肌和小肠中作为局部释放的LPL抑制剂,而来源于肝脏和脂肪组织的ANGPTL4主要作为调节全身脂质代谢的内分泌因子。作为一种多功能蛋白质,ANGPTL4还抑制巨噬细胞中泡沫细胞的形成,发挥抗动脉粥样硬化作用。ANGPTL4在内皮细胞中的功能仍不确定。由于ANGPTL4单克隆抗体的潜在副作用,其安全性需要进一步评估。结论ANGPTL4的生物学特性比遗传学研究结果复杂得多。未来的研究必须阐明如何在ANGPTL4靶向治疗的“黄金时间”到来之前,有效降低冠心病风险,同时避免潜在的动脉粥样硬化效应和其他并发症。

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