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Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2389-96. doi: 10.1161/ATVBAHA.113.302175. Epub 2013 Aug 15.

Overexpression of catalase in vascular smooth muscle cells prevents the formation of abdominal aortic aneurysms.

Author information

1
From the Department of Medicine, Cardiology Division, Emory University School of Medicine, Atlanta, GA (I.P., D.W., G.J., W.R.T.); Cardiology Division, Atlanta Veterans Affairs Medical Center, Atlanta, GA (W.R.T.); and Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (W.R.T.).

Abstract

OBJECTIVE:

Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species promotes the development of AAA remains unclear. Here, we investigate the effect of hydrogen peroxide (H2O2)-degrading enzyme catalase on the formation of AAA.

APPROACH AND RESULTS:

AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91 ± 0.1 versus 0.76 ± 0.09 mm). Similarly, in a transgenic mouse model, catalase overexpression in the vascular smooth muscle cells preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85 ± 0.14 versus 0.57 ± 0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacological administration or genetic overexpression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and vascular smooth muscle cell apoptosis was evident in aortas of catalase-overexpressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic overexpression of catalase in vascular smooth muscle cells did not alter the total aortic H2O2 levels.

CONCLUSIONS:

The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic vascular smooth muscle cell survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity.

KEYWORDS:

aortic aneurysm; catalase; hydrogen peroxide; inflammation; smooth muscle

PMID:
23950141
PMCID:
PMC3880803
DOI:
10.1161/ATVBAHA.113.302175
[Indexed for MEDLINE]
Free PMC Article

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