Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs

Doris M. Tham, Baby Martin-McNulty, Yi Xin Wang, Dennis W Wilson, Ronald Vergona, Mark E. Sullivan, William Dole, John C Rutledge

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Angiotensin II (ANG II) promotes vascular inflammation through nuclear factor-κB (NF-κB)-mediated induction of pro-inflammatory genes. The role of peroxisome proliferator-activated receptors (PPARs) in modulating vascular inflammation and atherosclerosis in vivo is unclear. The aim of the present study was to examine the effects of ANG II on PPARs and NF-κB-dependent pro-inflammatory genes in the vascular wall in an in vivo model of atherosclerosis and aneurysm formation. Six-month-old male apolipoprotein E-deficient (apoE-KO) mice were treated with ANG II (1.44 mg/kg per day for 30 days). ANG II enhanced vascular inflammation, accelerated atherosclerosis, and induced formation of abdominal aortic aneurysms. These effects of ANG II in the aorta were associated with downregulation of both PPAR-α and PPAR-γ mRNA and protein and an increase in transcription of monocyte chemotactic protein-1 (MCP-1), macrophage-colony stimulating factor (M-CSF), endothelial-selectin (E-selectin), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) throughout the entire aorta. ANG II also activated NF-κB with increases in both p52 and p65 NF-κB subunits. In summary, these in vivo results indicate that ANG II, through activation of NF-κB-mediated pro-inflammatory genes, promotes vascular inflammation, leading to acceleration of atherosclerosis and induction of aneurysm in apoE-KO mice. Downregulation of PPAR-α and -γ by ANG II may diminish the anti-inflammatory potential of PPARs, thus contributing to enhanced vascular inflammation.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalPhysiological Genomics
Volume11
StatePublished - Jan 2003

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Peroxisome Proliferator-Activated Receptors
Angiotensin II
Down-Regulation
Blood Vessels
Genes
Inflammation
Atherosclerosis
Apolipoproteins E
Aneurysm
Aorta
Selectins
Macrophage Colony-Stimulating Factor
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
Abdominal Aortic Aneurysm
Nitric Oxide Synthase Type II
Intercellular Adhesion Molecule-1
Cyclooxygenase 2
Anti-Inflammatory Agents
Messenger RNA

Keywords

  • Aneurysm
  • Atherosclerosis
  • Chemokines
  • Endothelial cell adhesion molecules

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs. / Tham, Doris M.; Martin-McNulty, Baby; Wang, Yi Xin; Wilson, Dennis W; Vergona, Ronald; Sullivan, Mark E.; Dole, William; Rutledge, John C.

In: Physiological Genomics, Vol. 11, 01.2003, p. 21-30.

Research output: Contribution to journalArticle

Tham, DM, Martin-McNulty, B, Wang, YX, Wilson, DW, Vergona, R, Sullivan, ME, Dole, W & Rutledge, JC 2003, 'Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs', Physiological Genomics, vol. 11, pp. 21-30.
Tham DM, Martin-McNulty B, Wang YX, Wilson DW, Vergona R, Sullivan ME et al. Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs. Physiological Genomics. 2003 Jan;11:21-30.
Tham, Doris M. ; Martin-McNulty, Baby ; Wang, Yi Xin ; Wilson, Dennis W ; Vergona, Ronald ; Sullivan, Mark E. ; Dole, William ; Rutledge, John C. / Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs. In: Physiological Genomics. 2003 ; Vol. 11. pp. 21-30.
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AU - Tham, Doris M.

AU - Martin-McNulty, Baby

AU - Wang, Yi Xin

AU - Wilson, Dennis W

AU - Vergona, Ronald

AU - Sullivan, Mark E.

AU - Dole, William

AU - Rutledge, John C

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N2 - Angiotensin II (ANG II) promotes vascular inflammation through nuclear factor-κB (NF-κB)-mediated induction of pro-inflammatory genes. The role of peroxisome proliferator-activated receptors (PPARs) in modulating vascular inflammation and atherosclerosis in vivo is unclear. The aim of the present study was to examine the effects of ANG II on PPARs and NF-κB-dependent pro-inflammatory genes in the vascular wall in an in vivo model of atherosclerosis and aneurysm formation. Six-month-old male apolipoprotein E-deficient (apoE-KO) mice were treated with ANG II (1.44 mg/kg per day for 30 days). ANG II enhanced vascular inflammation, accelerated atherosclerosis, and induced formation of abdominal aortic aneurysms. These effects of ANG II in the aorta were associated with downregulation of both PPAR-α and PPAR-γ mRNA and protein and an increase in transcription of monocyte chemotactic protein-1 (MCP-1), macrophage-colony stimulating factor (M-CSF), endothelial-selectin (E-selectin), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) throughout the entire aorta. ANG II also activated NF-κB with increases in both p52 and p65 NF-κB subunits. In summary, these in vivo results indicate that ANG II, through activation of NF-κB-mediated pro-inflammatory genes, promotes vascular inflammation, leading to acceleration of atherosclerosis and induction of aneurysm in apoE-KO mice. Downregulation of PPAR-α and -γ by ANG II may diminish the anti-inflammatory potential of PPARs, thus contributing to enhanced vascular inflammation.

AB - Angiotensin II (ANG II) promotes vascular inflammation through nuclear factor-κB (NF-κB)-mediated induction of pro-inflammatory genes. The role of peroxisome proliferator-activated receptors (PPARs) in modulating vascular inflammation and atherosclerosis in vivo is unclear. The aim of the present study was to examine the effects of ANG II on PPARs and NF-κB-dependent pro-inflammatory genes in the vascular wall in an in vivo model of atherosclerosis and aneurysm formation. Six-month-old male apolipoprotein E-deficient (apoE-KO) mice were treated with ANG II (1.44 mg/kg per day for 30 days). ANG II enhanced vascular inflammation, accelerated atherosclerosis, and induced formation of abdominal aortic aneurysms. These effects of ANG II in the aorta were associated with downregulation of both PPAR-α and PPAR-γ mRNA and protein and an increase in transcription of monocyte chemotactic protein-1 (MCP-1), macrophage-colony stimulating factor (M-CSF), endothelial-selectin (E-selectin), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) throughout the entire aorta. ANG II also activated NF-κB with increases in both p52 and p65 NF-κB subunits. In summary, these in vivo results indicate that ANG II, through activation of NF-κB-mediated pro-inflammatory genes, promotes vascular inflammation, leading to acceleration of atherosclerosis and induction of aneurysm in apoE-KO mice. Downregulation of PPAR-α and -γ by ANG II may diminish the anti-inflammatory potential of PPARs, thus contributing to enhanced vascular inflammation.

KW - Aneurysm

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