doxycycline does not influence established abdominal aortic aneurysms in angiotensin ii-infused mice强力霉素不影响建立了腹主动脉瘤血管紧张素ii-infused老鼠.pdfVIP

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms in Angiotensin II-Infused Mice 1,2 1 1 1 1 3 Xiaojie Xie , Hong Lu , Jessica J. Moorleghen , Deborah A. Howatt , Debra L. Rateri , Lisa A. Cassis , Alan Daugherty1,3* 1 Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States of America, 2 Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province, Department of Cardiology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, People’s Republic of China, 3 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky, United States of America Abstract Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum concentrations. Methods and Results: LDL receptor 2/ 2 male mice fed a saturated-fat supplemented diet were infused with AngII (1,000 ng/kg/min) via mini-osmotic pumps for 28 days. Upon verification of AAA formation by noninvasive high frequency ultrasonography, mice were stratified based on aortic lumen diameters, and continuously infu