Abstract 523: Diabetes Promotes the Development of Aortic Aneurysm in Mice with Hypertension
Introduction: The estimated prevalence of diabetes mellitus (DM) is 8.4% among adults in the U.S. Cardiovascular disease is a major complication of DM. We have observed that diabetic mice, but not non-diabetic mice, undergoing 2kidney-1clip (2K1C) surgery inducing renovascular hypertension had high mortality attributed to ruptured aortic aneurysm. However, the effect of diabetes on formation of aortic aneurysm remains unclear.
Method: In our previous experiment, 163 mice were divided into 4 groups: leptin KO 2K1C (db 2K1C, n=52), leptin KO Sham (db Sham, n=20), wild type 2K1C (dbc 2K1C, n=62), and wild type Sham (dbc Sham, n=29), respectively. We found that 42% (22/52) of db 2K1C died, from ruptured aortic aneurysms examined by gross examination, within 120 days, while others survived 100%. In this study, available H&E aortic sections of survived mice (n=74): db 2K1C (n=30), db Sham (n=15), dbc 2K1C (n=20), and dbc Sham (n=9) were examined 2K1C surgery in a blinded fashion. Aortic lesions defined as necrosis, thrombosis and dropped-out smooth muscle cells, which are signs of early formation of aortic aneurysm, were identified. Inflammation was graded as mild, moderate and severe inflammation.
Result: The db 2K1C mice had a significantly greater aortic lesions (16/30, 53%) compared to the db Sham (13/15, 20%); and dbc 2K1C mice (1/20, 5%), p=0.002 and 0.0001, respectively. The number of aortic lesions in the dbc 2K1C group was not statistically different from that of the dbc Sham group (p=0.5). Similarly, the number of aortic lesions in the db Sham group was not statistically different from that of the dbc Sham group (0/9, 0%), p=0.125. Moderate-to-severe inflammation in the tunica media was more prevalence in db mice than the dbc mice.
Conclusion: We report for the first time an increased incidence of aortic lesions in db 2K1C compared to dbc and sham groups. This finding suggests that diabetes contributes to aortic aneurysm formation in mice with renal artery stenosis, potentially due to induction of inflammation. Further studies to confirm a mechanism are warranted.
Author Disclosures: A. Wongjarupong: None. B.E. Knudsen: None. S. Hartono: None. J.P. Grande: None.
- © 2014 by American Heart Association, Inc.