Treatment With Simvastatin Suppresses the Development of Experimental Abdominal Aortic Aneurysms in Normal and Hypercholesterolemic Mice

Steinmetz, Éric; Buckley, Celine; Shames, Murray L.; Ennis, Terri L.; Vanvickle-Chavez, Sarah J.; Mao, Dongli; Goeddel, Lee A.; Hawkins, Cherady J.; Thompson, Robert W.

doi:10.1097/01.sla.0000150258.36236.e0

Cited by 154 publications

(62 citation statements)

References 63 publications

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“…elastase-induced AAAs, but that aneurysm development is suppressed by treatment with statins in both normal and Apo-E (−/−) mice. 51 This finding likely reflects the pleiotropic effects of statins acting to interfere with key inflammatory signaling pathways as a mechanism of suppressing aneurysmal degeneration. Recent clinical studies have also highlighted the potential benefits of treatment with statins in patients with AAAs.…”

Section: Elastase-induced Aaas In Genetically Altered Micementioning

confidence: 99%

Pathophysiology of Abdominal Aortic Aneurysms

Thompson

Curci

Ennis

et al. 2006

Annals of the New York Academy of Sciences

159

168

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Abdominal aortic aneurysms (AAAs) represent a complex degenerative disorder involving chronic aortic wall inflammation and destructive remodeling of structural connective tissue. Studies using human AAA tissues have helped identify a variety of molecular mediators and matrix-degrading proteinases, which contribute to aneurysm disease, thereby providing a sound foundation for understanding AAAs; however, these human tissue specimens represent only the "end stage" of a long and progressive disease process. Further progress in understanding the pathophysiology of AAAs is therefore dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. Based on original studies in rats, transient perfusion of the abdominal aorta with porcine pancreatic elastase has provided a reproducible and robust model of AAAs. More recent applications of this model to mice have also opened new avenues for investigation. In this review, we summarize investigations using the elastase-induced mouse model of AAAs including results in animals with targeted deletion of specific genes and more general differences in mice on different genetic backgrounds. These studies have helped us identify genes that are essential to the development of AAAs (such as MMP9, IL6, and AT1R) and to reveal other genes that may be dispensable in aneurysm formation. Investigations on mice from different genetic backgrounds are also beginning to offer a novel approach to evaluate the genetic basis for susceptibility to aneurysm development.

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Section: Elastase-induced Aaas In Genetically Altered Micementioning

confidence: 99%

Pathophysiology of Abdominal Aortic Aneurysms

Thompson

Curci

Ennis

et al. 2006

Annals of the New York Academy of Sciences

159

168

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“…Statins can reduce MMP secretion in cultured macrophages 14 and aneurysmal explants 15 . They have also been shown recently to suppress aneurysm expansion in normal and hypercholesterolaemic animal models, suggesting that their anti-inflammatory effects are independent of their lipid-lowering activity 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms

Abisi

Burnand

Humphries

et al. 2008

Journal of British Surgery

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“…Statins have potent LDL lowering effects via inhibition of the rate-limiting step in cholesterol synthesis. There are a number of experimental models which demonstrate the potential for treating the vasculature with statins to inhibit matrix formation [24,25], cellular proliferation [6] and vascular aneurysm formation [82]. Although valve replacement is the current treatment of choice for severe critical aortic stenosis, future insights into the mechanisms of calcification and its progression may indicate a role for lipid lowering therapy in modifying the rate of progression of stenosis.…”

Section: Development Of Future Medical Therapies For Calcific Aortic mentioning

confidence: 99%

Role of Oxidative Stress in Calcific Aortic Valve Disease: From Bench to Bedside - The Role of a Stem Cell Niche

Rajamannan¹

2013

Oxidative Stress and Chronic Degenerative Diseases - A Role for Antioxidants

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Treatment With Simvastatin Suppresses the Development of Experimental Abdominal Aortic Aneurysms in Normal and Hypercholesterolemic Mice

Cited by 154 publications

References 63 publications

Pathophysiology of Abdominal Aortic Aneurysms

Pathophysiology of Abdominal Aortic Aneurysms

Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms

Role of Oxidative Stress in Calcific Aortic Valve Disease: From Bench to Bedside - The Role of a Stem Cell Niche

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