Role of high-density lipoprotein and scavenger receptor B type I in the promotion of endothelial repair.
There is considerable experimental evidence that high-density lipoprotein (HDL) cholesterol and the principal high-affinity HDL receptor scavenger receptor B type I (SR-BI) afford cardiovascular protection. However, the fundamental mechanisms underlying the protection remain complex and not well understood. Recent work in cell culture indicates that the HDL-SR-BI tandem stimulates endothelial cell migration. Further studies have revealed that this entails Src-mediated, phosphatidylinositol 3-kinase-mediated, and mitogen-activated protein kinase-mediated signaling that leads to the activation of Rac guanosine triphosphate hydrolase and the resultant rearrangement of the actin cytoskeleton. Furthermore, assessment of reendothelialization after perivascular electric injury in mice indicates that HDL-SR-BI-mediated stimulation of endothelial migration is operative in vivo. Recent additional work in mice also indicates that HDL activates the recruitment of endothelial progenitor cells into the intimal layer in the setting of endothelial injury. As such, signaling initiated by HDL-SR-BI promotes endothelial repair, and this novel mechanism of action may be critically involved in the impact of the lipoprotein on vascular health and disease.
Mineo
Chieko
C
Division of Pulmonary and Vascular Biology, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. chieko.mineo@utsouthwestern.edu
Shaul
Philip W
PW
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D008076:Cholesterol, HDL / Q000378:metabolism; D004727:Endothelium / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D019001:Nitric Oxide Synthase; D051122:Scavenger Receptors, Class B / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D008076:Cholesterol, HDL; D020690:GTPase-Activating Proteins; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D019001:Nitric Oxide Synthase; D020744:rac GTP-Binding Proteins