Links lipoproteins to chronic kidney disease and atherosclerosis.
Links lipoproteins to chronic kidney disease and atherosclerosis.
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DOI：
10.1097/mol.0000000000000625
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发表时间：
2019-10
影响因子：
4.4
通讯作者：
Hong S. Lu;M. Kukida;A. Daugherty
中科院分区：
文献类型：
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作者：
Hong S. Lu;M. Kukida;A. Daugherty
DOI：10.1097/MOL.0000000000000625在慢性肾脏疾病患者中经常被报道[1，2]。也有越来越多的证据表明，慢性肾脏疾病会加速和加剧动脉粥样硬化[3-5]。这篇评论总结了最近发表的两篇文章：一篇文章报道了高密度脂蛋白蛋白质组与蛋白尿和动脉粥样硬化的关联[6&&]，另一篇文章显示抑制原蛋白转换酶枯草杆菌-克星9(PCSK9)改善了慢性肾脏疾病患者的心血管结局[7&&]。蛋白尿是糖尿病患者肾脏疾病发展和进展的一个标志，糖尿病患者也有很高的动脉粥样硬化风险。邵某等人。[6&&]从一项观察性队列研究EDIC(糖尿病干预和并发症流行病学)研究中提供了对1型糖尿病个体的全面分析。191例患者分为白蛋白排泄率正常组、微量白蛋白尿组(30~300 mg/d)和大量白蛋白尿组(300 mg/d)。串联质谱分析在所有参与者的高密度脂蛋白中检测到46种蛋白质。其中，微量白蛋白尿组和大量白蛋白尿组与白蛋白排泄率正常组比较，有7种蛋白质含量较高，7种蛋白质含量较低。在Logistic回归模型中，在调整了年龄、性别、吸烟、药物和一些代谢参数后，冠状动脉疾病患者的对氧磷酶(PON)1和PON3的丰度较低，与低密度脂蛋白和高密度脂蛋白的浓度无关。此外，PON1的低丰度与蛋白尿有关，而与PON3无关。这项研究提供的证据表明，与白蛋白排泄率正常的1型糖尿病患者相比，有蛋白尿的1型糖尿病患者的高密度脂蛋白蛋白质组具有特定的模式。然而，目前尚不清楚这种高密度脂蛋白蛋白质组与蛋白尿或动脉粥样硬化性疾病之间是否存在因果关系。血浆中高浓度的低密度脂蛋白胆固醇是动脉粥样硬化的独立危险因素[8，9]。Evocumab是一种针对PCSK9的人源性单抗，可降低血浆低密度脂蛋白-胆固醇
DOI:10.1097/MOL.0000000000000625 Dyslipidemia has been reported frequently in patients with chronic kidney disease [1,2]. There is also accumulating evidence that chronic kidney disease accelerates and augments atherosclerosis [3–5]. This commentary summarizes two recent publications: one article reported association of the HDL proteome with albuminuria and atherosclerosis [6 && ], and the other article showed that inhibition of proprotein convertase subtilisin-kexin type 9 (PCSK9) improved cardiovascular outcomes in patients with chronic kidney disease [7 && ]. Albuminuria is a marker that represents the development and progression of kidney disease in patients with diabetes, who also have high risk for atherosclerosis. Shao et al. [6 && ] provided comprehensive analyses on type 1 diabetes mellitus individuals from an observational cohort study, the EDIC (Epidemiology of Diabetes Interventions and Complications) study. One hundred and ninety-one patients were grouped as normal albumin excretion rate, microalbuminuria (30 to <300 mg/day), and macroalbuminuria ( 300 mg/day), respectively. Tandem mass spectrometric analyses detected 46 proteins in HDL in all participants. Among these proteins, seven proteinswere higher and sevenproteinswere lower in HDL isolated from individuals with microalbuminuria or macroalbuminuria, compared with individuals with normal albumin excretion rate. In a logistic regression model, after adjusting age, sex, smoking, medications, and some metabolic parameters, paraoxonase (PON)1 and PON3 had lower abundance in individuals with coronary artery disease, independent of LDL-cholesterol and HDL-cholesterol concentrations. In addition, low abundance of PON1, but not PON3, was associated with albuminuria. This study provided evidence that the HDL proteome had specific patterns in type 1 diabetic patients with albuminuria, compared with those having normal albumin excretion rates. However, it is unclear whether this HDL proteome has causal correlation with albuminuria or atherosclerotic disease. High plasma concentrations of LDL-cholesterol are an independent risk factor for atherosclerosis [8,9]. Evolocumab is a human monoclonal antibody targeting PCSK9 to reduce plasma LDL-cholesterol