Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France; Service de Biochimie, Pôle de biologie, Hôpital de Purpan, CHU de Toulouse, Toulouse, France.
Department of Endocrinology, Division of Lipid Disorders, Charité Universitätsmedizin Berlin, Berlin, Germany; Division of Endocrinology, Diabetology and Clinical Nutrition, Department of Internal Medicine 1, University of Kiel, Arnold Heller Straße 3, Kiel 24105, Germany.
Vascul Pharmacol. 2020 Dec;135:106804. doi: 10.1016/j.vph.2020.106804. Epub 2020 Sep 25.
Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9-I) have been reported to cause a moderate increase in high-density lipoprotein (HDL) cholesterol in human studies. We thus evaluated the effect of two approved PCSK9-I on the concentration and lipid composition of HDL particle subclasses.
95 patients (62.8 ± 10.3 years old, 58% men), with or without statin and/or ezetimibe treatment and eligible for PCSK9-I therapy, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). Their HDL particle profiles were measured by NMR spectroscopy at baseline and after 4 weeks of PCSK9-I treatment.
PCSK9-I treatment increased the level of HDL-C by 7%. The level of medium-sized HDL particles (M-HDL-P) increased (+8%) while the level of XL-HDL-P decreased (-19%). The lipid core composition was altered in the smaller S- and M-HDL-P, with a reduction in triglycerides (TG) and an enrichment in cholesterol esters (CE), whereas the for the larger XL- and L-HDL-P the relative CE content decreased and the TG content increased. Ezetimibe therapy differentially impacted the HDL particle distribution, independently of statin use, with an increase in S-HDL-P in patients not receiving ezetimibe.
As S- and M-HDL-P levels are inversely related to cardiovascular risk, PCSK9-I treatment may result in a more atheroprotective HDL particle profile, particularly in patients not concomitantly treated with ezetimibe.
在人体研究中，前蛋白转化酶枯草溶菌素/克那霉 9 抑制剂（PCSK9-I）已被报道可使高密度脂蛋白（HDL）胆固醇适度增加。因此，我们评估了两种已批准的 PCSK9-I 对 HDL 颗粒亚类浓度和脂质组成的影响。
95 名患者（62.8±10.3 岁，58%为男性），无论是否使用他汀类药物和/或依折麦布治疗，且符合 PCSK9-I 治疗条件，接受依洛尤单抗（140mg）或阿利西尤单抗（75 或 150mg）治疗。在 PCSK9-I 治疗前和治疗后 4 周，通过 NMR 光谱法测量他们的 HDL 颗粒谱。
PCSK9-I 治疗使 HDL-C 水平升高 7%。中等大小的 HDL 颗粒（M-HDL-P）水平升高（+8%），而 XL-HDL-P 水平降低（-19%）。较小的 S-和 M-HDL-P 的脂质核心组成发生改变，甘油三酯（TG）减少，胆固醇酯（CE）增加，而较大的 XL-和 L-HDL-P 的相对 CE 含量减少，TG 含量增加。依折麦布治疗独立于他汀类药物的使用而对 HDL 颗粒分布产生不同影响，未接受依折麦布治疗的患者 S-HDL-P 增加。
由于 S-和 M-HDL-P 水平与心血管风险呈负相关，因此 PCSK9-I 治疗可能导致更具抗动脉粥样硬化作用的 HDL 颗粒谱，特别是在未同时接受依折麦布治疗的患者中。
