Momtazi Amir Abbas, Banach Maciej, Pirro Matteo, Stein Evan A, Sahebkar Amirhossein
Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran.
Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz 90-549, Poland.
Drug Discov Today. 2017 Jun;22(6):883-895. doi: 10.1016/j.drudis.2017.01.006. Epub 2017 Jan 19.
Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of type 2 DM (T2DM), genetic findings have shown contradictory results. Overall, the impact of PCSK9 inhibitors on glycemic control parameters in patients with DM remains unclear. Here, we assess the available evidence for the association of PCSK9 status with the incidence and control of DM in preclinical and clinical studies, and identify molecular mechanisms regulating PCSK9 expression in the diabetic state.
糖尿病(DM)与心血管疾病(CVD)风险增加相关。前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)抑制剂已成为有效的降低低密度脂蛋白胆固醇的化合物。尽管现有流行病学、临床前和临床研究结果表明血浆PCSK9水平与血糖参数及2型糖尿病(T2DM)风险呈正相关,但遗传学研究结果却相互矛盾。总体而言,PCSK9抑制剂对DM患者血糖控制参数的影响仍不明确。在此,我们评估临床前和临床研究中PCSK9状态与DM发病率及控制情况相关性的现有证据,并确定糖尿病状态下调节PCSK9表达的分子机制。