| Autor: |
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, Eckardstein, Arnold von |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Apr2024, Vol. 120 Issue 5, p476-489, 14p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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