A. Mesa1, S. Rahimpour2, N. Fernandez1, L. Song1, S. M. Pham2, K. A. Webster1, V. Gupta3, R. I. Vazquez-Padron1 1University Of Miami,Miami, FL, USA 2University Of Maryland,Baltimore, MD, USA 3Rush University Medical Center,Chicago, IL, USA
Introduction:
Atherosclerosis is a chronic systemic disease characterized by the accumulation of lipids and leukocytes in the arterial intima which eventually lead to myocardial infarction and other detrimental vascular events. New investigations revealed the role of integrin Mac-1 in leukocyte adhesion, migration and recruitment during the development of vascular proliferative diseases.
Methods:
In this study, a novel Mac-1 agonist drug named leukadherins (LA-1) is used as an innovative therapeutic tool to control inflammation with the ultimate goal to diminish atherogenesis. To test our hypothesis, daily intraperitoneal LA-1 or vehicle (control) injections (10 mg/ml) were administered to 20 hypercholesterolemic mice (ApoE null mice) kept in high fat diet for 16 weeks.
Results:
Mice treated with LA-1 exhibited a significantly reduction of monocytes and pro-inflammatory molecules in blood (p ≤ 0.001). Assessment of aortic atherosclerosis burden of treated and control mice indicated that LA-1 treatment significantly decreased atherosclerotic development (p = 0.03). Additionally, the results suggested that LA-1 reduces inflammation by retaining monocytes in bone marrow and spleen given that treated mice showed a significant reclusion of monocytes in these primary hematopoietic organs (p ≤ 0.001).
Conclusion:
These results suggest LA-1 treatment via Mac-1 activation represents a novel agonist approach for treating vascular inflammation and atherosclerosis.