Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration

Atherosclerosis. 2009 Jan;202(1):34-40. doi: 10.1016/j.atherosclerosis.2008.03.020. Epub 2008 Apr 6.

Abstract

Recently, atherosclerosis has been considered to be the result of inflammation. Interestingly, hydroxymethylglutaryl-coenzyme (HMG-Co) A inhibitors (statins), which are clinically used as lipid-lowering agents, have been reported to have various anti-inflammatory effects. As abdominal aortic aneurysm (AAA) is a common degenerative condition associated with atherosclerosis, this study was designed to investigate the inhibitory effect of a statin, atorvastatin, on aneurysm formation apart from its lipid-lowering effect. We employed an elastase-induced rat AAA model, as statins do not lower cholesterol in rats. Mean aneurysm diameter was significantly smaller in the atorvastatin treatment group as compared to control at 4 weeks after surgery (P<0.05). Interestingly, atorvastatin inhibited the expression of ICAM and MCP-1, followed by the suppression of macrophage recruitment into the aortic wall at 1 week after operation. A significant reduction in MMP-12, but not MMP-2, -3 and -9, expression was also observed by treatment with atorvastatin at 1 week after surgery. In addition, synthesis of collagen and elastin in the vascular wall were significantly increased by atorvastatin. Here, the present study demonstrated a direct effect of atorvastatin to inhibit the progression of aortic aneurysm, independent of its lipid-lowering effect. This study suggests new therapeutic aspects of statins to inhibit the progression of aneurysms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Atorvastatin
  • Cell Movement
  • Collagen / metabolism
  • Disease Models, Animal
  • Heptanoic Acids / metabolism
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Inflammation
  • Macrophages / metabolism*
  • Pancreatic Elastase / metabolism
  • Pyrroles / metabolism
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Collagen
  • Atorvastatin
  • Pancreatic Elastase