Original ArticleThe Angiotensin Receptor Blocker, Azilsartan Medoxomil (TAK-491), Suppresses Vascular Wall Expression of Plasminogen Activator Inhibitor Type-I Protein Potentially Facilitating the Stabilization of Atherosclerotic PlaquesFrench, Christopher J MD; Zaman, A.K.M Tarikuz MBBS; Sobel, Burton E MDAuthor Information From the Department of Medicine, Cardiovascular Research Institute, University of Vermont, Burlington, VT. Received for publication January 11, 2011; accepted April 3, 2011. Supported by Takeda Pharmaceutical Company Limited. C.J. French was supported in part by a Hemostasis and Thrombosis Training Program, K.G. Mann T32, HL07594. The authors declare no conflicts of interest. Reprints: Christopher French, MD, Cardiovascular Research Institute, University of Vermont, Colchester Research Facility, 208 South Park Drive, Colchester 05446, VT (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: August 2011 - Volume 58 - Issue 2 - p 143-148 doi: 10.1097/FJC.0b013e31821dcbea Buy Metrics Abstract Increased expression of plasminogen activator inhibitor type-I (PAI-1) in vessel walls seems to accelerate atherosclerosis. Angiotensin II can increase the synthesis of PAI-1. Inhibition of this process may facilitate migration of vascular smooth muscle cells (VSMCs) stabilizing atherosclerotic plaques. To determine whether the inhibition of the angiotensin II type 1 receptor can blunt the expression of PAI-1 protein in the aortic wall, we administered azilsartan medoxomil (AZL-M), a prodrug of an angiotensin II type 1 receptor blocker developed by the Takeda Pharmaceutical Company Limited, for 16 weeks to ApoE knockout mice on a high fat diet rendered overexpressors of PAI-1 in VSMCs. Homogenates of the pooled aortas from each group were assayed for PAI-1 by enzyme-linked immunosorbent assay. Cellularity of atherosclerotic lesions was assessed by 4′,6-diamidino-2-phenylindole staining in sections of aortic lesions, and collagen content in the lesions was quantified by immunohistochemistry. Aortic wall PAI-1 was decreased by each of the 3 dosage regimens of AZL-M (0.1-10 mg/kg). Cellularity and collagen were increased in lesions from mice given AZL-M, consistent with the development of more stable plaques. Accordingly, the suppression of PAI-1 expression by AZL-M may attenuate the evolution of atherosclerotic plaques vulnerable to rupture. Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.