Angiotensin II stimulates endothelial integrin beta3 expression via nuclear factor-kappaB activation

Exp Aging Res. 2006 Jan-Mar;32(1):47-60. doi: 10.1080/01902140500325049.

Abstract

The present study examined the effect and part mechanism of angiotensin II-stimulated integrin beta3 gene expression in human umbilical vein endothelial cells. Protein level and mRNA level of integrin beta3 expression were determined using enzyme-linked immunoadsorbent assay and reverse transcription-polymerase chain reaction. Four plasmids of 5'-different deletion of integrin beta3 gene promoter were constructed to transiently transfected into cells to uncover the region in response to angiotensin II. Blockade of nuclear factor-kappaB (NF-kappaB) signaling pathway effect on integrin beta3 expression was analyzed by cotransfection with mutant plasmids for NF-kappaB-inducing kinase, inhibitory proteins alpha and beta of NF-kappaB kinase, respectively, together with the integrin beta3 plasmid including the sequence -1486 approximately - 900. The study found that 10(-8) mol/L,10(-7) mol/L, 10(-6) mol/L, and 10(-5) mol/L angiotensin II increased integrin beta(3) protein level by 45%, 52%, 62%, and 73% respectively. Angiotensin II at 10(-6) mol/L increased integrin beta3 mRNA level by 67%. The luciferase activity of the integrin beta3 plasmid PGL3 - 1486 approximately - 900 increased by 84.72% in response to angiotensin II. N-acetylcysteine blocked angiotensin II-induced NF-kappaB activity and integrin beta3 expression. Blockade of NF-kappaB signaling pathway abolished the stimulation of angiotensin II. These results suggest that angiotensin II stimulates integrin beta3 expression partly by NF-kappaB activation.

MeSH terms

  • Acetylcysteine / pharmacology
  • Angiotensin II / pharmacology*
  • Cells, Cultured
  • Endothelium, Vascular / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Integrin beta3 / biosynthesis*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Plasmids / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Integrin beta3
  • NF-kappa B
  • RNA, Messenger
  • Vasoconstrictor Agents
  • Angiotensin II
  • Acetylcysteine