Abstract 13050: Genetic Deletion of Integrin Alpha1beta1 Alleviates Aortic Rupture in Angiotensin II-induced Abdominal Aortic Aneurysm
Introduction: Abdominal aortic aneurysm (AAA) is a common disease characterized by chronic inflammation and degradation of extracellular matrix. Integrin alpha1beta1 is a major collagen receptor that is expressed on activated monocytes and involved as well as smooth muscle cells and fibroblasts. Integrin alpha1beta1 play an impotent role in the regulation of feedback inhibition of collagen synthesis in vessel wall. We investigated the role of integrin alpha1beta1 using murine angiotensin II-induced AAA model in which alpha1 integrin was deficient.
Methods: Apolipoprotein E -/- mice that were either alpha1 +/+ or alpha1 -/-, were infused with either saline or angiotensin II (1000 ng/kg per minute) for 28 days via mini-osmotic pumps.
Results: An increase in systolic blood pressure was observed equivalently in both groups. Deficiency in integrin aplha1 did not reduce the external diameters after 28 day (1.6 ± 0.29 mm [alpha1 +/+] vs. 1.73 ± 0.69 mm [alpha1 -/-], p=NS)(Fig A). Interestingly, Kaplan-Meier survival curves revealed that the alpha1 -/- mice (n=36) were decreased in death due to aortic rupture compared to the alpha1 +/+ mice (n=36) (p=0.04, Fig B). Next, quantitative real time PCR was performed at day 7 and at day 28. The increase in IL-6 in aortae at day 7 in the alpha1 +/+ was significantly reduced in the alpha1 -/- group. Matrix metalloproteinase (MMP)-2 and MMP-9 in aortae were increased at day both in the alpha1 -/- and the alpha1 +/+ groups similarly. Of note, increase in type 1 collagen at day 7 in the alpha1 -/- was significantly greater than that in the alpha1+/+.
Conclusions: Our results suggest that Integrin alpha1beta1 is involved in susceptibility to aortic rupture in angiotensin II-induced AAA by the suppression of inflammation and the augmentation of collagen synthesis.
Author Disclosures: T. Miyoshi: None. T. Yonezawa: None. M. Yoshida: None. S. Akagi: None. Y. Saito: None. K. Nakamura: None. H. Ito: None.
- © 2014 by American Heart Association, Inc.