Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export.

Mads Fuglsang Kjølby; Olav Michael Andersen; Tilman Breiderhoff; Anja Nawarecki Fjorback; Karen-Marie Pedersen; Peder Søndergaard Madsen; Pernille Jansen; Jörg Heeren; Thomas Willnow; Anders Nykjær

Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export.

Mads Fuglsang Kjølby, Olav Michael Andersen, Tilman Breiderhoff, Anja Nawarecki Fjorback, Karen-Marie Pedersen, Peder Søndergaard Madsen, Pernille Jansen, Jörg Heeren, Thomas Willnow, Anders Nykjær

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

232 Citationer (Scopus)

Abstract

Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3.
Udgivelsesdato: september 8

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	12
Nummer	3
Sider (fra-til)	213-223
Antal sider	11
ISSN	1550-4131
Status	Udgivet - 2010

Citationsformater

@article{e784787002cb11e083f5000ea68e967b,

title = "Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export.",

abstract = "Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8",

author = "Kj{\o}lby, {Mads Fuglsang} and Andersen, {Olav Michael} and Tilman Breiderhoff and Fjorback, {Anja Nawarecki} and Karen-Marie Pedersen and Madsen, {Peder S{\o}ndergaard} and Pernille Jansen and J{\"o}rg Heeren and Thomas Willnow and Anders Nykj{\ae}r",

note = "Paper id:: 20816088",

year = "2010",

language = "English",

volume = "12",

pages = "213--223",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export.

AU - Kjølby, Mads Fuglsang

AU - Andersen, Olav Michael

AU - Breiderhoff, Tilman

AU - Fjorback, Anja Nawarecki

AU - Pedersen, Karen-Marie

AU - Madsen, Peder Søndergaard

AU - Jansen, Pernille

AU - Heeren, Jörg

AU - Willnow, Thomas

AU - Nykjær, Anders

N1 - Paper id:: 20816088

PY - 2010

Y1 - 2010

N2 - Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8

AB - Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8

M3 - Journal article

SN - 1550-4131

VL - 12

SP - 213

EP - 223

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -