Inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation

Biomed Pharmacother. 2009 Dec;63(10):754-61. doi: 10.1016/j.biopha.2009.02.006. Epub 2009 Mar 10.


Recent evidence indicates that renin-angiotensin system (RAS) plays an important role in the pathogenesis of atherosclerosis. It was reported that inhibition of RAS with angiotensin II type 1 receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs) is effective in prevention of atherosclerosis. Here, we investigated the effects of an ARB or/and an ACEI on atherosclerosis development and periadventitial inflammation in apolipoprotein E (ApoE)-deficient mice. RT-PCR revealed that major RAS components were expressed in periaortic tissue. Ang II infusion significantly increased accumulation of bone marrow derived cells into both neointima (p<0.05) and periaortic tissue (p<0.01). Male ApoE- deficient mice were treated with either vehicle, TA606A (10mg/kg/day, ARB), imidapril (3mg/kg/day, ACEI) or TA606A plus imidapril (TA606A 10mg/kg/day+imidapril 3mg/kg/day, ARB+ACEI) for 24 weeks starting at 12 weeks of age. ARB, ACEI, and ARB+ACEI significantly reduced atherosclerotic lesion formation in aorta compared with vehicle (p<0.05), with reduced expression of monocyte chemoattractant protein-1 in periaortic tissues (p<0.01). Neither blood pressure nor heart rate was changed by the treatments at these lower doses. Imidapril significantly reduced lipid deposition in atheroma and plasminogen activator inhibitor-1 expression in periadventitial tissue (p<0.05, respectively). Imidapril and combination therapy significantly attenuated macrophage infiltration into the atherosclerotic plaque (p<0.05, respectively). All treatments reduced macrophage accumulation in the periadventitial tissue 12 weeks after treatment (p<0.05, respectively). These results suggest that inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / pathology
  • Apolipoproteins E / genetics*
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control
  • Chemokine CCL2 / genetics
  • Connective Tissue / drug effects
  • Connective Tissue / pathology
  • Gene Expression Regulation / drug effects
  • Imidazoles / pharmacology
  • Imidazolidines / pharmacology
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Male
  • Mice
  • Mice, Knockout
  • Pyridines / pharmacology
  • Renin-Angiotensin System / drug effects*
  • Tetrazoles / pharmacology


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Apolipoproteins E
  • Chemokine CCL2
  • Imidazoles
  • Imidazolidines
  • Pyridines
  • TA 606
  • Tetrazoles
  • imidapril