Lysyl Oxidase Inhibition Ablates Sexual Dimorphism of Abdominal Aortic Aneurysm Formation in Mice
Michihiro Okuyama, Weihua Jiang, Aida Javidan, Jeff Zheying Chen, Deborah A. Howatt, Lihua Yang, Mika Hamaguchi, Takumi Yasugi, Jun Aono, Roberto I. Vázquez-Padrón, Venkateswaran Subramanian
Abstract
angiotensin II aortic aneurysm, abdominal protein-lysine 6-oxidase sex characteristics Editorial, see p 1901 A bdominal aortic aneurysm (AAA) formation involves a complex process of aortic medial destruction through degradation of extracellular matrix proteins, elastin, and collagen. AAA exhibits sexual dimorphism because male sex is a major risk factor of AAA in both mice and humans. During aortic development, lysyl oxidase (LOX) covalently cross-links elastin and collagen to create an insoluble extracellular matrix resistant to proteolytic degradation. We hypothesized that testosterone-mediated suppression of LOX activity is a critical contributor to increased susceptibility of male to AAA formation. Ethics and institutional review board approvals were provided by University of Kentucky (Protocol-2011-0907) and the Ehime University (Protocol-1603002), and informed consent was received from all participants.