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

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
Massimiliano RuscicaLaura Calabresi

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 con...Continue Reading

Citations

Nov 28, 2018·European Journal of Preventive Cardiology·Chiara MacchiMassimiliano Ruscica
Jul 9, 2020·Journal of Clinical Medicine·Maria Francesca GrecoMassimiliano Ruscica
May 21, 2020·Nutrients·Maria Pia AdorniNicola Ferri
Aug 18, 2020·The American Journal of Pathology·Chiara MacchiMassimiliano Ruscica

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