Afanasieva Olga, Ezhov Marat V, Klesareva Elena, Razova Oksana, Chubykina Uliana, Egiazaryan Mane, Sherstyuk Ekaterina, Afanasieva Marina, Utkina Elena, Pokrovsky Sergei
Institute of Experimental Cardiology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552 Moscow, Russia.
AL Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552 Moscow, Russia.
J Cardiovasc Dev Dis. 2020 Oct 15;7(4):45. doi: 10.3390/jcdd7040045.
The aim of this study was to investigate the influence of a single injection of Evolocumab on the dynamics of Lp(a), fractions of apoB100-containing lipoproteins, PCSK9, and their complexes in healthy individuals with elevated Lp(a) levels. This open-label, 4-week clinical study involved 10 statin-naive volunteers with Lp(a) >30 mg/dL, LDL-C < 4.9 mmol/L, and a moderate risk of cardiovascular events. The concentrations of Lp(a), lipids, PCSK9, circulating immune complexes (CIC), and plasma complexes of PCSK9 with apoB100-containing lipoproteins (Lp(a)-PCSK9 and LDL-PCSK9) were measured before and each week after Evolocumab (MABs) administration. After a single dose injection of 140 mg of MABs, the median concentration of PCSK9 in serum increased from 496 to 3944 ng/mL; however, the entire pool of circulating PCSK9 remained bound with MABs for 2-3 weeks. LDL-C level decreased significantly from 3.36 mmol/L to 2.27 mmol/L during the first two weeks after the injection. Lp(a) concentrations demonstrated multidirectional changes in different patients with the maximal decrease on the second week. There were no positive correlations between the changes in levels of Lp(a), LDL-C, and TC. The change in the amount of circulating complex of PCSK9-Lp(a) was significantly less than of PCSK9-apoB100 (-5% and -47% after 1 week, respectively). A single administration of monoclonal antibodies against PCSK9 (Evolocumab) in healthy individuals with hyperlipoproteinemia(a) resulted in a decrease of Lp(a) of 14%, a 5% decrease in PCSK9-Lp(a), a 36% reduction of LDL-C, a 47% decrease in PCSK9-apoB100 and a tenfold increase in total serum PCSK9 concentration.
本研究的目的是调查单次注射依洛尤单抗对Lp(a)水平升高的健康个体中Lp(a)的动态变化、含载脂蛋白B100的脂蛋白组分、前蛋白转化酶枯草溶菌素9（PCSK9）及其复合物的影响。这项开放标签的4周临床研究纳入了10名未服用过他汀类药物的志愿者，其Lp(a)>30mg/dL，低密度脂蛋白胆固醇（LDL-C）<4.9mmol/L，且有中度心血管事件风险。在注射依洛尤单抗（单克隆抗体）之前以及之后每周测量Lp(a)、血脂、PCSK9、循环免疫复合物（CIC）以及PCSK9与含载脂蛋白B100的脂蛋白（Lp(a)-PCSK9和低密度脂蛋白-PCSK9）的血浆复合物的浓度。单次注射140mg单克隆抗体后，血清中PCSK9的中位浓度从496ng/mL增加到3944ng/mL；然而，循环中的PCSK9整体与单克隆抗体结合了2至3周。注射后的前两周内，LDL-C水平从3.36mmol/L显著降至2.27mmol/L。Lp(a)浓度在不同患者中呈现多方向变化，在第二周下降幅度最大。Lp(a)、LDL-C和总胆固醇（TC）水平的变化之间没有正相关关系。PCSK9-Lp(a)循环复合物量的变化明显小于PCSK9-载脂蛋白B100（1周后分别为-5%和-47%）。在患有高脂蛋白血症（a）的健康个体中单次注射抗PCSK9单克隆抗体（依洛尤单抗）导致Lp(a)降低14%，PCSK9-Lp(a)降低5%，LDL-C降低36%，PCSK9-载脂蛋白B100降低47%，血清总PCSK9浓度增加了10倍。
