Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders

Massimiliano Ruscica, Sara Simonelli, Margherita Botta, Alice Ossoli, Maria Giovanna Lupo, Paolo Magni, Alberto Corsini, Marcello Arca, Livia Pisciotta, Fabrizio Veglia, Guido Franceschini, Nicola Ferri, Laura Calabresi

Research output: Contribution to journalArticlepeer-review

Abstract

Proprotein convertase subtilisin/kexin 9 (PCSK9), a protein regulating the number of cell-surface LDL receptors (LDLR), circulates partially associated to plasma lipoproteins. How this interaction alters PCSK9 plasma levels is still unclear. In the present study, we took advantage of the availability of a large cohort of carriers of genetic HDL disorders to evaluate how HDL defects affect plasma PCSK9 levels and its distribution among lipoproteins. Plasma PCSK9 concentrations were determined by ELISA in carriers of mutations in LCAT, ABCA1, or APOAI genes, and lipoprotein distribution was analyzed by FPLC. Carriers of one or two mutations in the LCAT gene show plasma PCSK9 levels comparable to that of unaffected family controls (homozygotes, 159.4 ng/mL (124.9;243.3); heterozygotes, 180.3 ng/mL (127.6;251.5) and controls, 190.4 ng/mL (146.7;264.4); P for trend = 0.33). Measurement of PCSK9 in plasma of subjects carrying mutations in ABCA1 or APOAI genes confirmed normal values. When fractionated by FPLC, PCSK9 peaked in a region between LDL and HDL in control subjects. In carriers of all HDL defects, lipoprotein profile shows a strong reduction of HDL, but the distribution of PCSK9 was superimposable to that of controls. In conclusion, the present study demonstrates that in genetically determined low HDL states plasma PCSK9 concentrations and lipoprotein distribution are preserved, thus suggesting that HDL may not be involved in PCSK9 transport in plasma.

Original languageEnglish
Pages (from-to)991-997
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1863
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

Keywords

  • Genetic HDL disorders
  • High-density lipoproteins
  • Lecithin:cholesterol acyltransferase
  • Proprotein convertase subtilisin/kexin 9

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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