Doxycycline does not influence established abdominal aortic aneurysms in angiotensin II-infused mice

• Published in: PloS one Vol. 7; no. 9; p. e46411
• Main Authors: Xie, Xiaojie, Lu, Hong, Moorleghen, Jessica J, Howatt, Deborah A, Rateri, Debra L, Cassis, Lisa A, Daugherty, Alan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-09-2012; Public Library of Science (PLoS)
• Subjects: Abdomen; Abdominal aortic aneurysm; Administration, Oral; Aneurysms; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Angiotensins; Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Aorta; Aorta, Abdominal - drug effects; Aorta, Abdominal - pathology; Aortic Aneurysm, Abdominal - complications; Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - pathology; Aortic aneurysms; Aortic Rupture - drug therapy; Aortic Rupture - etiology; Aortic Rupture - pathology; Atherosclerosis; Biology; Blood Pressure; Cardiovascular disease; Care and treatment; Cholesterol; Cholesterol - blood; Diet, High-Fat; Disease Models, Animal; Dosage and administration; Doxycycline; Doxycycline - pharmacology; Drinking water; Drug therapy; Health aspects; High frequencies; Infusion Pumps, Implantable; Laboratories; Low density lipoprotein; Male; Medicine; Mice; Mice, Knockout; Prevention; Receptors, LDL - deficiency; Receptors, LDL - genetics; Rodents; Rupture; Rupturing; Ultrasonic imaging; Ultrasound; Ultrasound imaging; Vasoconstrictor Agents - pharmacology; United States > US; Kentucky
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046411

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.
LDL receptor -/- 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 infused with AngII while also administered either vehicle or doxycycline (100 mg/kg/day) in drinking water for 56 days. Administration of doxycycline led to serum drug concentrations of 2.3 ± 0.6 µg/ml. Doxycycline administration had no effect on serum cholesterol concentrations and systolic blood pressures. Doxycycline administration did not prevent progressive aortic dilation as determined by temporal measurements of lumen dimensions using high frequency ultrasound. This lack of effect on AAA regression and progression was confirmed at the termination of the study by ex vivo measurements of maximal width of suprarenal aortas and AAA volumes. Also, doxycycline did not reduce AAA rupture. Medial and adventitial remodeling was not overtly changed by doxycycline as determined by immunostaining and histological staining.
Doxycycline administration did not influence AngII-induced AAA progression and aortic rupture when administered to mice with established AAAs.