title: Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration.
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.
authors.affiliation: Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Shiraya
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyake
authors.forename: Motokuni
authors.initials: M
authors.lastname: Aoki
authors.forename: Fujiwara
authors.initials: F
authors.lastname: Yoshikazu
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Ohgi
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: 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
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D003094:Collagen; D000069059:Atorvastatin; D010196:Pancreatic Elastase