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


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.
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.).
Ioannis
I
Parastatidis
Daiana
D
Weiss
Giji
G
Joseph
W Robert
WR
Taylor
D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D017209:Apoptosis; D002122:Calcium Chloride; D002374:Catalase / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D018836:Inflammation Mediators; D012333:RNA, Messenger; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride
aortic aneurysm; catalase; hydrogen peroxide; inflammation; smooth muscle