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 language | English |
|---|---|
| Pages (from-to) | 991-997 |
| Number of pages | 7 |
| Journal | Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids |
| Volume | 1863 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
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Keywords
- Genetic HDL disorders
- High-density lipoproteins
- Lecithin:cholesterol acyltransferase
- Proprotein convertase subtilisin/kexin 9
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders. / Ruscica, Massimiliano; Simonelli, Sara; Botta, Margherita; Ossoli, Alice; Lupo, Maria Giovanna; Magni, Paolo; Corsini, Alberto; Arca, Marcello; Pisciotta, Livia; Veglia, Fabrizio; Franceschini, Guido; Ferri, Nicola; Calabresi, Laura.
In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1863, No. 9, 01.09.2018, p. 991-997.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Plasma PCSK9 levels and lipoprotein distribution are preserved in carriers of genetic HDL disorders
AU - Ruscica, Massimiliano
AU - Simonelli, Sara
AU - Botta, Margherita
AU - Ossoli, Alice
AU - Lupo, Maria Giovanna
AU - Magni, Paolo
AU - Corsini, Alberto
AU - Arca, Marcello
AU - Pisciotta, Livia
AU - Veglia, Fabrizio
AU - Franceschini, Guido
AU - Ferri, Nicola
AU - Calabresi, Laura
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
KW - Genetic HDL disorders
KW - High-density lipoproteins
KW - Lecithin:cholesterol acyltransferase
KW - Proprotein convertase subtilisin/kexin 9
UR - http://www.scopus.com/inward/record.url?scp=85047825627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047825627&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2018.05.015
DO - 10.1016/j.bbalip.2018.05.015
M3 - Article
AN - SCOPUS:85047825627
VL - 1863
SP - 991
EP - 997
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
SN - 1388-1981
IS - 9
ER -