The interrelations between PCSK9 metabolism and cholesterol synthesis and absorption

被引：19

作者：

Silbernagel, Guenther ^{[1
,3
]}

Steiner, Lars K. ^{[1
]}

Hollstein, Tim ^{[3
,4
]}

Fauler, Guenter ^{[2
]}

Scharnagl, Hubert ^{[2
]}

Stojakovic, Tatjana ^{[2
]}

Schumann, Friederike ^{[3
]}

Boeluekbasi, Bediha ^{[5
]}

Maerz, Winfried ^{[2
,6
,7
]}

Steinhagen-Thiessen, Elisabeth ^{[3
]}

Laufs, Ulrich ^{[8
]}

Kassner, Ursula ^{[3
]}

机构：

[1] Med Univ Graz, Dept Internal Med, Div Angiol, A-8036 Graz, Austria

[2] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria

[3] Charite Univ Med Berlin, Campus Virchow Klinikum, Lipid Clin, Interdisciplinary Metab Ctr, D-13353 Berlin, Germany

[4] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix Indian Med Ctr, Phoenix, AZ 85016 USA

[5] Univ Klinikum Saarlandes, Klin Innere Med Kardiol Angiol & Internist Intens, D-66421 Homburg, Germany

[6] Heidelberg Univ, Mannheim Med Fac, Dept Internal Med Nephrol Hypertensiol Endocrinol, D-68167 Mannheim, Germany

[7] Synlab Holding Germany GmbH, Synlab Acad, D-68161 Mannheim, Germany

[8] Univ Klinikum Leipzig, Klin & Poliklin Kardiol, D-04103 Leipzig, Germany

来源：

JOURNAL OF LIPID RESEARCH | 2019年 / 60卷 / 01期

关键词：

cholesterol/absorption; cholesterol/biosynthesis; cholesterol metabolism; clinical trials; low density lipoprotein; proprotein convertase subtilisin/kexin type 9; SUBTILISIN/KEXIN TYPE 9; CORONARY-HEART-DISEASE; REDUCING LIPIDS; ALL-CAUSE; EVOLOCUMAB; ATORVASTATIN; EFFICACY; STEROLS; SAFETY; RISK;

D O I：

10.1194/jlr.P088583

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Very few studies have investigated the interrelations between proprotein convertase subtilisin/kexin type 9 (PCSK9) metabolism, cholesterol synthesis, and cholesterol absorption. We aimed to address this issue in a large clinical trial of 245 patients with hypercholesterolemia. Serum lipids, PCSK9, lathosterol (cholesterol synthesis marker), campesterol, and sitosterol (cholesterol absorption markers) were measured before and 4-8 weeks after the start of treatment with PCSK9-antibodies (alirocumab or evolocumab). The patients had mean (standard error) LDL-cholesterol and PCSK9 concentrations of 3.87 (0.10) mmol/l and 356 (17) ng/ml, respectively. Eighty-four patients received no lipid-lowering pretreatment, 26 ezetimibe, 38 statins, and 97 ezetimibe + statins. Circulating PCSK9 increased in parallel with the potency of lipid-lowering pretreatment with circulating PCSK9 being highest in the ezetimibe + statin group (P < 0.001). Treatment with PCSK9-antibodies strongly decreased LDL-cholesterol, lathosterol, campesterol, and sitosterol (all P < 0.001) but hardly affected noncholesterol sterol to cholesterol ratios. Lipid-lowering pretreatment was not associated with the effects of PCSK9-antibodies on noncholesterol sterols (all P > 0.05). Summing up, circulating PCSK9 is increased by cholesterol synthesis and absorption inhibitors. Increased PCSK9 expression may partly explain the strong reductions of LDL-cholesterol achieved with PCSK9-antibodies after such pretreatment. On the other hand, treatment with PCSK9-antibodies does not significantly change the balance between cholesterol synthesis and absorption.

引用

页码：161 / 167

页数：7

共 28 条

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