Murine model of surgically induced acute aortic dissection type A.
OBJECTIVE
This study aimed at developing a murine model of surgically induced acute aortic dissection type A for investigation of the formation and progression of acute aortic dissection and to test whether this system could be used for biomarker discovery.


METHODS
Adult fibrillin-1 deficient, Fbn1(C1039G/+) mice and wild-type mice were anesthetized, ventilated, and the ascending aorta exposed via hemisternotomy. We hypothesized that acute aortic dissection could be induced either by injecting autologous blood into the aortic wall or by injury to the wall with aortic clamping. Echocardiography was done preoperatively, and serum samples were collected before and 30 minutes after the operation and analyzed by enzyme-linked immunosorbent assay.


RESULTS
Echocardiography revealed larger aortic root diameters in Fbn1(C1039G/+) compared with wild-type mice (P = .001). Histologic examination showed that aortic clamp injury but not injection of blood leads to large intimal tears, disruption of aortic wall structures, and localized dissection of the aortic media in Fbn1(C1039G/+) mice. Acute aortic dissection developed in 4 of 5 Fbn1(C1039G/+) mice versus 0 of 5 wild-type mice after aortic clamping (P < .01). Elastin staining showed higher elastic fiber fragmentation and disarray in Fbn1(C1039G/+) compared with wild-type mice. Enzyme-linked immunosorbent assay analysis revealed elevated circulating transforming growth factor beta1 concentrations after induction of acute aortic dissection in Fbn1(C1039G/+) mice (P = .02, 150 +/- 61 ng/mL vs 456 +/- 97 ng/mL), but not in wild-type or sham-operated mice.


CONCLUSIONS
Aortic clamp injury can induce AAD in Fbn1(C1039G/+), but not in wild-type mice. This murine model of surgically induced acute aortic dissection is highly reproducible and nonlethal in the short term. Using this system, we revealed that circulating transforming growth factor beta1 is a promising biomarker for acute aortic dissection.
Matt
Peter
P
Division of Cardiac Surgery, University Hospital Basel/Berne, Spitalstrasse 21, CH-4031 Basel, Switzerland. pmatt@uhbs.ch
Huso
David L
DL
Habashi
Jennifer
J
Holm
Tammy
T
Doyle
Jeff
J
Schoenhoff
Florian
F
Liu
Guosheng
G
Black
James
J
Van Eyk
Jennifer E
JE
Dietz
Harry C
HC
D000208:Acute Disease; D000784:Aortic Dissection / Q000097:blood* / Q000209:etiology; D000818:Animals; D001014:Aortic Aneurysm / Q000097:blood* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000097:blood*
D015415:Biomarkers; D053773:Transforming Growth Factor beta1