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Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of high-density lipoproteins and low-density lipoproteins in opposite ways.
Velagapudi, Srividya; Wang, Dongdong; Poti, Francesco; Feuerborn, Renata; Robert, Jerome; Schlumpf, Eveline; Yalcinkaya, Mustafa; Panteloglou, Grigorios; Potapenko, Anton; Simoni, Manuela; Rohrer, Lucia; Nofer, Jerzy-Roch; von Eckardstein, Arnold.
Afiliação
  • Velagapudi S; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Wang D; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Poti F; Department of Medicine and Surgery-Unit of Neurosciences, University of Parma, Parma, Italy.
  • Feuerborn R; Department of Biomedical, Metabolic and Neural Sciences-Unit of Endocrinology, University of Modena and Reggio Emilia, Modena, Italy.
  • Robert J; Central Laboratory Facility, University Hospital of Münster, Münster, Germany.
  • Schlumpf E; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Yalcinkaya M; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Panteloglou G; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Potapenko A; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Simoni M; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • Rohrer L; Department of Biomedical, Metabolic and Neural Sciences-Unit of Endocrinology, University of Modena and Reggio Emilia, Modena, Italy.
  • Nofer JR; Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
  • von Eckardstein A; Central Laboratory Facility, University Hospital of Münster, Münster, Germany.
Cardiovasc Res ; 120(5): 476-489, 2024 Apr 30.
Article em En | MEDLINE | ID: mdl-38109696
ABSTRACT

AIMS:

The entry of lipoproteins from blood into the arterial wall is a rate-limiting step in atherosclerosis. It is controversial whether this happens by filtration or regulated transendothelial transport.Because sphingosine-1-phosphate (S1P) preserves the endothelial barrier, we investigated in vivo and in vitro, whether S1P and its cognate S1P-receptor 3 (S1P3) regulate the transendothelial transport of lipoproteins. METHODS AND

RESULTS:

Compared to apoE-haploinsufficient mice (CTRL), apoE-haploinsufficient mice with additional endothelium-specific knock-in of S1P3 (S1P3-iECKI) showed decreased transport of LDL and Evan's Blue but increased transport of HDL from blood into the peritoneal cave. After 30 weeks of high-fat diet feeding, S1P3-iECKI mice had lower levels of non-HDL-cholesterol and less atherosclerosis than CTRL mice. In vitro stimulation with an S1P3 agonist increased the transport of 125I-HDL but decreased the transport of 125I-LDL through human aortic endothelial cells (HAECs). Conversely, inhibition or knock-down of S1P3 decreased the transport of 125I-HDL but increased the transport of 125I-LDL. Silencing of SCARB1 encoding scavenger receptor B1 (SR-BI) abrogated the stimulation of 125I-HDL transport by the S1P3 agonist. The transendothelial transport of 125I-LDL was decreased by silencing of SCARB1 or ACVLR1 encoding activin-like kinase 1 but not by interference with LDLR. None of the three knock-downs prevented the stimulatory effect of S1P3 inhibition on transendothelial 125I-LDL transport.

CONCLUSION:

S1P3 regulates the transendothelial transport of HDL and LDL oppositely by SR-BI-dependent and SR-BI-independent mechanisms, respectively. This divergence supports a contention that lipoproteins pass the endothelial barrier by specifically regulated mechanisms rather than passive filtration.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transporte Proteico / Células Endoteliais / Aterosclerose / Receptores de Esfingosina-1-Fosfato / Lipoproteínas HDL / Lipoproteínas LDL Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transporte Proteico / Células Endoteliais / Aterosclerose / Receptores de Esfingosina-1-Fosfato / Lipoproteínas HDL / Lipoproteínas LDL Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article