Abstract 398: Hydrogen Peroxide Mediates Calcium Chloride--Induced Aortic Wall Dilatation
Rationale: Abdominal aneurysm formation is characterized by infiltration of the aortic wall with inflammatory cells, activation of proteolytic enzymes, loss of vascular smooth muscle cells (VSMC), and neovascularization. It is also known that hydrogen peroxide (H2O2) plays an important role in these processes.
Hypothesis: Since H2O2 participates in the pathophysiologic processes that govern aneurysmal dilatation, we hypothesized that scavenging of H2O2 with catalase protects against the formation of aortic aneurysms.
Methods: To assess our hypothesis 3 groups of mice, all 8-10-week-old males on the C57BL6 background, were used. Aortic dilatation was induced with the application of CaCl2 on the infrarenal aortas. We compared the aortic dilation in mice that specifically over-express catalase in the VSMC (group 1) or in the myeloid cell lineage (MCL) (group 2) with their wild type littermates. Chemical injury with CaCl2 was also induced in wild type mice which were treated with continuous intravenous infusion of PEG-catalase or saline for 8 weeks (group 3). The aortic diameter was measured with a caliper and with videomicroscopy on the day of surgery and 8 weeks later. H2O2 levels were quantified with the Amplex Red assay.
Results: Application of CaCl2 resulted in a significant increase in H2O2 generation in the infrarenal aortas compared to saline controls, which peaked on post-operative day 10 (0.60±0.09 vs. 0.37±0.05 μM/aortic ring, n=3/grp, p=0.02). Compared to their wild type littermates, mice that over-express catalase in the VSMC had negligible dilation of the aorta (0.78±0.05 vs. 0.53±0.02 mm, n=7/grp, p=0.001). Similarly, over-expression of catalase in MCL protected against aortic dilation (0.76±0.02 vs. ±0.005 mm, n=7, p<0.0001). Corroborating the above findings, continuous intravenous infusion of PEG-catalase, but not saline, protected from CaCl2 induced aortic dilation (0.73±0.03 vs.0.56±0.02 mm, n=3-6/grp, p=0.007).
Conclusions: Our data suggest that H2O2 is essential in CaCl2 induced aortic aneurysm formation.
- © 2012 by American Heart Association, Inc.