Homocysteine upregulates vascular cell adhesion molecule-1 expression in cultured human aortic endothelial cells and enhances monocyte adhesion

Matthew D. Silverman, Ramagopal J. Tumuluri, Mishel Davis, Gladys Lopez, James T. Rosenbaum, Peter I. Lelkes

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Elevated plasma homocysteine is an independent risk factor for atherosclerosis. We hypothesized that homocysteine enhances monocyte/human aortic endothelial cell (HAEC) interactions, a pivotal early event in atherogenesis, by upregulating endothelial adhesion molecules. After incubation of cultured HAECs with reduced DL-homocysteine for up to 24 hours, adhesion of human monocytes to homocysteine-stimulated HAECs was significantly upregulated in a time- and dose-dependent fashion. Pretreatment of HAECs with 100 μmol/L homocysteine caused a 4.5-fold increase in the adhesion of normal human monocytes (P<0.001). Similarly, adhesion of monocytic U937 cells was maximally elevated by 3.5-fold at 100 μmol/L homocysteine (P<0.001). In support of our hypothesis, vascular cell adhesion molecule (VCAM)-1 mRNA expression increased 5-fold in HAECs after 3 hours of treatment with 100 μmol/L homocysteine, as assessed by quantitative reverse transcription-polymerase chain reaction. Neutralizing antibody studies confirmed the involvement of VCAM-1 in mediating monocyte adhesion to homocysteine-stimulated HAECs. Coincubation of HAECs with homocysteine and tumor necrosis factor-α synergistically elevated monocyte adhesion as well as VCAM-1 protein expression, with the latter evaluated by flow cytometry. Preincubation of HAECs with cyclooxygenase inhibitors completely abrogated homocysteine-induced monocyte adhesion, whereas scavenging reactive oxygen species and the elevation of NO caused partial inhibition only. These data support the notion that the proinflammatory effects of homocysteine may have important implications in atherogenesis.

Original languageEnglish (US)
Pages (from-to)587-592
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number4
DOIs
StatePublished - Apr 29 2002
Externally publishedYes

Keywords

  • Cyclooxygenase
  • Homocysteine
  • Human aortic endothelial cells
  • Monocyte adhesion
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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