Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration.
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.
Shiraya
Suguru
S
Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Japan.
Miyake
Takashi
T
Aoki
Motokuni
M
Yoshikazu
Fujiwara
F
Ohgi
Shigetsugu
S
Nishimura
Motonobu
M
Ogihara
Toshio
T
Morishita
Ryuichi
R
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D003094:Collagen; D000069059:Atorvastatin; D010196:Pancreatic Elastase