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.
Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders / M. Ruscica, S. Simonelli, M. Botta, A. Ossoli, M.G. Lupo, P. Magni, A. Corsini, M. Arca, L. Pisciotta, F. Veglia, G. Franceschini, N. Ferri, L. Calabresi. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. - ISSN 1388-1981. - 1863:9(2018 Sep), pp. 991-997.
|Titolo:||Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders|
RUSCICA, MASSIMILIANO (Primo) [Writing – Original Draft Preparation]
SIMONELLI, SARA (Secondo) [Methodology]
BOTTA, MARGHERITA [Methodology]
OSSOLI, ALICE FEDERICA [Methodology]
MAGNI, PAOLO [Visualization]
CORSINI, ALBERTO [Supervision]
CALABRESI, LAURA (Ultimo) [Writing – Original Draft Preparation] (Corresponding)
|Parole Chiave:||Proprotein convertase subtilisin/kexin 9; High-density lipoproteins; Genetic HDL disorders; Lecithin:cholesterol acyltransferase|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||set-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bbalip.2018.05.015|
|Appare nelle tipologie:||01 - Articolo su periodico|