Abstract 252: Chronic Relaxin Treatment Does Not Augment Angiotensin II Induced Aortic Pathologies in Mice

Introduction: Human relaxin is being tested clinically as an acute treatment for heart failure. The effects of relaxin on extracellular matrix remodeling, among several mechanisms, may provide myocardial benefit, however, the effects of relaxin on vascular extracellular matrix-related pathology has not been examined. Human aortic aneurysm is characterized by extracellular remodeling, as well as inflammation, thrombus formation and rupture. Studying relaxin in a model of aortic aneurysm might provide insight into mechanisms of the disease but also will assess whether such agents impact the incidence/severity of aortic aneurysms (AA). Objectives: The purpose of this study was to test the effects of relaxin, an anti-fibrotic agent, on angiotensin II (AngII)-induced AA, which is characterized by enhanced activation of matrix metalloproteinases (MMPs); additionally this model mimics human pathology. Methods and Results: Vehicle or relaxin was co-infused with AngII (1.44 mg/kg/d) in either C57BL/6 mice or apoE null mice through mini osmotic pumps for 28 days. Dose-dependent plasma relaxin concentrations were noted (12-60ng/ml). Relaxin did not augment AngII-induced aortic rupture rate, the most severe consequence of AA. Maximal ex vivo diameters of suprarenal aortas were measured for abdominal aortic dilation, and ascending aortic area was measured using an en face method to determine ascending aortic dilation. Maximal aortic diameter of suprarenal aortas did not show significant difference in relaxin and AngII infused mice with either mouse strain. Relaxin also had no effect on ascending aortic dilation in both mouse strains. Conclusion: Chronic relaxin infusion for 28days does not augment aortic aneurysms in AngII-infused mice, suggesting relaxin might not impact other matrix-dependent vascular pathologies, if used as a treatment for heart failure, although additional studies are warranted. Ongoing studies interrogate the potential benefits of molecular mechanisms of relaxin response in the AngII-induced aortic pathologies.