Pharmacologically induced thoracic and abdominal aortic aneurysms in mice.
Aortic aneurysms are common among the elderly population. A large majority of aortic aneurysms are located at two distinct aneurysm-prone regions, the abdominal aorta and thoracic aorta involving the ascending aorta. In this study, we combined two factors that are associated with human aortic aneurysms, hypertension and degeneration of elastic lamina, to induce an aortic aneurysm in mice. Roles of hemodynamic conditions in the formation of aortic aneurysms were assessed using two different methods for inducing hypertension and antihypertensive agents. In 9-week-old C57BL/6J male mice, hypertension was induced by angiotensin II or deoxycorticosterone acetate-salt hypertension; degeneration of elastic lamina was induced by infusion of beta-aminopropionitrile, a lysyl oxidase inhibitor. Irrespective of the methods for inducing hypertension, mice developed thoracic and abdominal aortic aneurysms (38% to 50% and 30 to 49%, respectively). Aneurysms were found at the two aneurysm-prone regions with site-specific morphological and histological characteristics. Treatment with an antihypertensive agent, amlodipine, normalized blood pressure and dramatically reduced aneurysm formation in the mice that received angiotensin II and beta-aminopropionitrile. However, treatment with captopril, an angiotensin-converting enzyme inhibitor, did not affect blood pressure or the incidence of aortic aneurysms in the mice that received deoxycorticosterone acetate-salt and beta-aminopropionitrile. In summary, we have shown that a combination of hypertension and pharmacologically induced degeneration of elastic laminas can induce both thoracic and abdominal aortic aneurysms with site-specific characteristics. The aneurysm formation in this model depended on hypertension but not on direct effects of angiotensin II to the vascular wall.
Kanematsu
Yasuhisa
Y
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94110, USA.
Kanematsu
Miyuki
M
Kurihara
Chie
C
Tsou
Tsung-Ling
TL
Nuki
Yoshitsugu
Y
Liang
Elena I
EI
Makino
Hiroshi
H
Hashimoto
Tomoki
T
D000629:Aminopropionitrile; D017311:Amlodipine / Q000627:therapeutic use; D000784:Aortic Dissection / Q000139:chemically induced / Q000473:pathology; D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008901:Mineralocorticoids / Q000627:therapeutic use; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors
D000959:Antihypertensive Agents; D008901:Mineralocorticoids; D000804:Angiotensin II; D000629:Aminopropionitrile; D017311:Amlodipine; D003900:Desoxycorticosterone; D008249:Protein-Lysine 6-Oxidase