Oxidized low-density lipoproteins facilitate leukocyte adhesion to aortic intima without affecting endothelium-dependent relaxation: Role of P-selectin

A. Mehta, B. Yang, S. Khan, J. B. Hendricks, C. Stephen, J. L. Mehta

Research output: Contribution to journalArticle

Abstract

Inflammatory cell deposition in atherosclerotic blood vessels has been thought to relate to loss of endothelium-derived nitric oxide (NO). To examine whether cell deposition correlates temporally with the loss of NO activity, rat aortic rings were incubated with buffer, native LDL (n-LDL), oxidized LDL (ox-LDL), or the endothelium-derived relaxing factor synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) for 2 hours, and vascular contractile response to norepinephrine and relaxant response to acetylcholine, thrombin, and calcium ionophore A23,187 were examined. Thereafter, the rings were exposed to biotin-fluorescein isothiocyanate labeled fluorescent or unlabeled leukocytes for 30 minutes. Cell adhesion was quantitated by fluorescent microscopy as well as by scanning electron microscopy. Incubation with n-LDL or ox-LDL did not affect either the contractile or the relaxant response of rings. However, leukocyte adhesion increased markedly in all ox-LDL-treated rings but not in those treated with n-LSL. Thus, leukocyte adhesion occurred independent of NO activity. In keeping with this concept, pretreatment of rings with the NO precursor L- arginine failed to influence leukocyte adhesion to rings incubated with ox- LDL. Treatment of rings with L-NAME also resulted in adhesion of a large number of leukocytes. Furthermore, all rings treated with ox-LDL or L-NAME demonstrated marked expression of P-selectin leukocyte adhesion molecules, determined by immunohistochemistry. Pretreatment of rings with the P-selectin blocking antibody PBL3 markedly decreased deposition of leukocytes in rings exposed to ox-LDL. These data show that cell adhesion to vascular intima exposed to ox-LDL shows no temporal relation with attenuation of NO activity, although inhibition of NO synthesis leads to leukocyte deposition. P-selectin expression on vascular rings exposed to ox-LDL appears to be the basis of leukocyte deposition.

Original languageEnglish (US)
Pages (from-to)2076-2083
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume15
Issue number11
StatePublished - 1995
Externally publishedYes

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Keywords

  • leukocytes
  • low-density lipoproteins
  • nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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