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      The role of lysyl oxidase family members in the stabilization of abdominal aortic aneurysms.

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          Abstract

          Abdominal aortic aneurysms (AAAs) are a major cause of morbidity and mortality in the United States today. We employed a model for AAA development using apolipoprotein E knock out mice fed a high-fat diet and treated with ANG II and β-aminopropionitrile (β-APN) for 4 wk. ANG II induces hypertension and atherosclerotic disease, whereas β-APN inhibits the activity of the lysyl oxidase/ lysyl oxidase-like protein (LOX/LOXL) family members. LOX/LOXL family members crosslink collagen and elastin in the extracellular matrix and therefore contribute to the integrity and stabilization of a healthy vessel wall. In this model, cotreatment with ANG II and β-APN caused a 90% AAA incidence and increased atherosclerotic lesion formation from less than 5% to greater than 25% after 4 wk. In more atheroprotected mouse strains (C57BL/6 and BalbC), cotreatment with ANG II and β-APN caused 50% and 40% AAA incidence, respectively. These data demonstrate the importance of LOX/LOXL to the stability of the vessel wall. Therapeutic strategies to overexpress LOX/LOXL enzymes or to support the crosslinking of soluble matrix proteins in a polymeric scaffold are a promising opportunity to achieve stabilization of AAAs.

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          Author and article information

          Journal
          Am. J. Physiol. Heart Circ. Physiol.
          American journal of physiology. Heart and circulatory physiology
          American Physiological Society
          1522-1539
          0363-6135
          Oct 15 2012
          : 303
          : 8
          Affiliations
          [1 ] Division of Cardiology Department of Medicine, Emory University School of Medicine Atlanta, Georgia 30322, USA.
          Article
          ajpheart.00217.2012
          10.1152/ajpheart.00217.2012
          3469640
          22904155
          871af0a6-417a-44c9-adfd-e90627f9f21d
          History

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