Abstract 115: Adventitial Fibroblast Depletion of AT1a Receptors Attenuates AngII-Induced Ascending and Abdominal Aortic Aneurysms in Hyperlipidemic Mice
Introduction and Objectives: Infusion of angiotensin II (AngII) into mice induces aneurysm formation and accelerates atherosclerosis. These pathologies are ablated by whole body deficiency of angiotensin II type 1a (AT1a) receptors. It is currently unknown which cell type is stimulated by AngII through AT1a receptors to augment either pathology. Surprisingly, depletion of AT1a receptors in macrophages, endothelium, and smooth muscle has minimal effects. Advential fibroblasts have been implicated in vascular inflammation. The current study examined the effect of deletion of AT1a receptors in fibroblasts on AngII-induced pathologies.
Methods and Results: LDL receptor -/- mice with fibroblast-specific deletion of AT1a receptors were produced by breeding hemizygous male mice expressing Cre under control of the S100A4 promoter to female AT1aR floxed mice. At 8 weeks of age, male, non-Cre littermates (N=13) and AT1a receptor x Cre-S100A4 (N=18) mice were fed a fat-enriched diet for 1 week before and during AngII infusion (1,000 ng/kg/min) for 28 days. AngII-infusion increased systolic blood pressures that were not influenced by fibroblast-specific deletion of AT1a receptors. AngII-induced expansion of the ascending aorta and abdominal aortic width were attenuated significantly in mice with fibroblast-specific AT1a receptor depletion (P=0.04 and P=0.043, respectively). In contrast, fibroblast-specific depletion of AT1a receptors had no effect on AngII-augmented atherosclerosis.
Conclusion: Fibroblast-specific deficiency of AT1a receptors is the first cell type that has been identified to attenuate AngII-induced aortic aneurysms.
Author Disclosures: D.L. Rateri: None. D.A. Howatt: None. A. Balakrishnan: None. J.J. Moorleghen: None. L.A. Cassis: None. A. Daugherty: None.
- © 2014 by American Heart Association, Inc.