Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia

Yu Kataoka, Mariko Harada-Shiba, Kazuhiro Nakao, Takahiro Nakashima, Shoji Kawakami, Masashi Fujino, Tomoaki Kanaya, Toshiyuki Nagai, Yoshio Tahara, Yasuhide Asaumi, Mika Hori, Masatsune Ogura, Yoichi Goto, Teruo Noguchi, Satoshi Yasuda

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties. Objective To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH. Methods About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated. Results Mature PCSK9 level was positively associated with percent atheroma volume (PAV: r = 0.78, P = .003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11–1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level <2.6 mmol/L, greater PAV was still observed in association with an elevated mature PCSK9 level (P = .003). Conclusions Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease. These findings suggest the potential role of mature PCSK9 in propagation of coronary atherosclerosis in HeFH.

Original languageEnglish
Pages (from-to)413-421.e3
JournalJournal of Clinical Lipidology
Volume11
Issue number2
DOIs
Publication statusPublished - 2017 Mar
Externally publishedYes

Keywords

  • Coronary atherosclerosis
  • Heterozygous familial hypercholesterolemia
  • Intravascular ultrasound
  • Proprotein convertase subtilisin/kexin type 9

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia'. Together they form a unique fingerprint.

Cite this