Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of HDL and LDL in opposite ways

Velagapudi S
December 18, 2023
Cardiovasc Res
https://pubmed.ncbi.nlm.nih.gov/38109696/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38109696/

Research summary

This study investigates the role of sphingosine-1-phosphate receptor 3 (S1P₃) in regulating the transendothelial transport of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Using an endothelium-specific inducible S1P₃ Knockin mouse model, researchers demonstrated that S1P₃ enhances HDL transport via a scavenger receptor class B type I (SR-BI)-dependent mechanism while inhibiting LDL transport through an SR-BI-independent pathway. These opposing effects suggest that S1P₃ plays a crucial role in maintaining endothelial barrier function and lipid homeostasis.

Key outcome of the study

S1P₃ differentially regulates the transendothelial transport of HDL and LDL, promoting HDL transport via SR-BI and inhibiting LDL transport through an SR-BI-independent mechanism, highlighting its potential as a therapeutic target in atherosclerosis.

Mouse model

Endothelium-specific inducible S1P₃ Knockin mouse model, generated by inserting the S1pr3 cDNA into the Rosa26 locus with a LoxP-STOP-LoxP (LSL) cassette, and crossed with VE-cadherin-CreERT2 mice to achieve endothelial-specific expression upon tamoxifen induction.

TARGET:
S1pr3
Sphingosine-1-phosphate receptor 3, EDG-3

Keywords

Atherosclerosis, Endothelial function, Lipid metabolism, Sphingosine-1-phosphate signaling

Technical specifications

Rosa26 Knockin, Conditional gene expression, Endothelial-specific expression, LoxP-STOP-LoxP cassette, Tamoxifen-inducible Cre system

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Quick KI mouse

The Rosa26 and Hprt gene loci are well suited for gene over-expression, reduced development time and cost with ready-to-use targeting vectors.