High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I

Divya Seetharam, Chieko Mineo, Andrew K. Gormley, Linda L. Gibson, Wanpen Vongpatanasin, Ken L. Chambliss, Lisa D. Hahner, Melissa L. Cummings, Richard L. Kitchens, Yves L. Marcel, Daniel J. Rader, Philip W. Shaul

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

Vascular disease risk is inversely related to circulating levels of high-density lipoprotein (HDL) cholesterol. However, the mechanisms by which HDL provides vascular protection are unclear. The disruption of endothelial monolayer integrity is an important contributing factor in multiple vascular disorders, and vascular lesion severity is tempered by enhanced endothelial repair. Here, we show that HDL stimulates endothelial cell migration in vitro in a nitric oxide-independent manner via scavenger receptor B type I (SR-BI)-mediated activation of Rac GTPase. This process does not require HDL cargo molecules, and it is dependent on the activation of Src kinases, phosphatidylinositol 3-kinase, and p44/42 mitogen-activated protein kinases. Rapid initial stimulation of lamellipodia formation by HDL via SR-BI, Src kinases, and Rac is also demonstrable. Paralleling the in vitro findings, carotid artery reendothelialization after perivascular electric injury is blunted in apolipoprotein A-I-/- mice, and reconstitution of apolipoprotein A-I expression rescues normal reendothelialization. Furthermore, reendothelialization is impaired in SR-BI-/- mice. Thus, HDL stimulates endothelial cell migration via SR-BI-initiated signaling, and these mechanisms promote endothelial monolayer integrity in vivo.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalCirculation research
Volume98
Issue number1
DOIs
StatePublished - Jan 1 2006

Keywords

  • Endothelium
  • High-density lipoprotein
  • Migration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Seetharam, D., Mineo, C., Gormley, A. K., Gibson, L. L., Vongpatanasin, W., Chambliss, K. L., Hahner, L. D., Cummings, M. L., Kitchens, R. L., Marcel, Y. L., Rader, D. J., & Shaul, P. W. (2006). High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I. Circulation research, 98(1), 63-72. https://doi.org/10.1161/01.RES.0000199272.59432.5b