Mouse model of heterotopic aortic arch transplantation.
BACKGROUND
Syngeneic heterotopic transplantation of segments of descending thoracic aortas containing atherosclerotic lesions from hypercholesterolemic mice into normocholesterolemic recipients has been useful for studies on plaque regression and stabilization. Because lesion development is more rapid and exuberant in the aortic arch, a technique of transplantation of the mouse aortic arch was developed.


METHODS
C57BL/6, apoE-deficient (apoE-/-) (hypercholesterolemic) mice were fed a Western diet for 22 weeks and used as donors of aortic-arch segments containing atherosclerotic lesions. Twenty syngeneic transplants were performed on age-matched wild-type (normocholesterolemic) mice. Aortic arches containing atherosclerotic lesions were implanted on the abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Two weeks after transplantation, grafts were noninvasively imaged in vivo by magnetic resonance (MR) microscopy. Grafts harvested four weeks after transplantation were submitted for histological examination.


RESULTS
All recipients survived the entire follow-up period (1 month) without complications. Duration of recipient procedure ranged from 90 to 120 (mean, 105) min; aortic clamping time varied from 45 to 60 min. In vivo MR microscopy demonstrated patency of the grafts and wall thickening that corresponded to the preexisting atherosclerotic lesions. Histology confirmed patency and atherosclerotic thickening of the grafts, and showed no evidence of acute tissue damage.


CONCLUSIONS
Syngeneic transplantation of the aortic arch in mice represents a useful alternative model for studies on morphology, imaging, and mechanisms of atherosclerosis. The curvature of the aortic arch is preserved after implantation onto the abdominal aorta, providing clear landmarks for noninvasive assessment using MR.
Chereshnev
Igor
I
Department of Medicine and the Zena and Michael Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Trogan
Eugene
E
Omerhodzic
Sabina
S
Itskovich
Vitalii
V
Aguinaldo
Juan-Gilberto
JG
Fayad
Zahi A
ZA
Fisher
Edward A
EA
Reis
Ernane D
ED
D000818:Animals; D001012:Aorta, Abdominal; D001013:Aorta, Thoracic / Q000473:pathology / Q000637:transplantation*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000473:pathology*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000235:genetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016042:Transplantation, Heterotopic
D001057:Apolipoproteins E