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首页> 外文期刊>Circulation journal >High-density lipoproteins - Multifunctional but vulnerable protections from atherosclerosis
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High-density lipoproteins - Multifunctional but vulnerable protections from atherosclerosis

机译：高密度脂蛋白-多功能但易受动脉粥样硬化损害的保护

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摘要

Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk.
机译：低血浆高密度脂蛋白（HDL）胆固醇水平与冠心病（CAD）的风险增加有关。 HDL颗粒在体内和体外具有许多作用，可以保护动脉免受化学或生物伤害或促进损伤修复。然而，HDL尚未成功地用于治疗。造成这种短缺的一个潜在原因是HDL颗粒的结构和功能复杂性，HDL颗粒携带80多种不同的蛋白质和200多种脂质，以及数种microRNA和其他潜在的生物活性分子。这种生理异质性在几种会增加心血管疾病风险的炎性疾病中进一步增加，包括CAD本身，还有糖尿病，慢性肾脏疾病和风湿性疾病。生物标志物HDL-胆固醇不能恢复蛋白质组和脂质组的定量和定性修饰，以及由此导致的功能丧失或功能障碍。到目前为止，正常和功能异常的HDL的许多生理和病理活动对于动脉粥样硬化的发病机理的相对重要性尚不清楚。这个问题的答案以及与HDL相关分子的结构功能关系的详细知识，是开发HDL来开发抗动脉粥样硬化药物以及诊断性生物标记物以进行识别，个性化治疗分层的先决条件，并监测心血管风险增加的患者。

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