Collagen Alterations in the Dissecting Aortic Aneurysm (DAA) Caused by N-(2-Aminoethyl) Ethanolamine (AEEA) in Rat
Ya Xu, Gracie Vargas, Paul J Boor. University of Texas Medical Branch, Galveston, TX
Background: The industrial chemical N-(2-aminoethyl) ethanolamine (AEEA) induces dissecting aortic aneurysm (DAA) in newborn rats following in utero exposure. To extend our knowledge about the severe deleterious effects of AEEA on normal vascular development, we aim to study the extracellular matrix changes during the formation of developmental DAA.
Design: We treated pregnant Sprague-Dawley rat dams with AEEA by gavage on gestation day (GD) 14-20, a period of rapid aortic development (Doses: 10, 50, 100 and 150 mg/kg/day; controls received saline only). Aortas from fetuses on GD 20 and from newborn pups (day 1) were examined by histopathology. Total collagen in aorta of fetuses from dam treated with AEEA (150 mg/kg/day) was examined by multiphoton fluorescence (MPF) and second harmonic generation (SHG) microscopy. Collagen types 1 & 3 distribution and quantization in aorta were further studied by immunohistochemistry and native western blot respectively.
Results: GD 20 fetuses showed no lesions. Extensive DAA was found in 100% of newborn pups (post natal day 1) in the two highest dose groups (100 and 150 mg/kg/day). Mediastinal hemorrhage, dissection in pulmonary artery and carotid artery were also found. A lesion grading system was devised; a dose-reponse was demonstrated for severity of lesion grade with AEEA dosage. Multiphoton fluorescence (MPF) and second harmonic generation (SHG) microscopy showed total collagen in aorta of GD 20 fetuses from treated dams was decreased. GD 20 fetuses from treated dams showed a decreased content of medial and adventitial collagen types 1 & 3 in aorta by immunohistochemistry; this decrease was confirmed by native western blot in pooled aortas. Collagen types 1 & 3 in AEEA treated group significantly decreased 34% and 30% respectively. There was no significant change of collagen types 1 & 3 of skin in AEEA treated group compared to the control, indictating that the collagen pathophysiology induced by AEEA exposure is specific for aorta and not a generalized phenomenon.
Conclusions: The pathologic mechanism of AEEA induced developmental DAA may be related to decreased collagen types 1 & 3 weakening the vascular wall. DAA induced by AEEA is a reproducible model that is useful to study the underlying mechanisms of DAA development in vivo.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 58, Wednesday Morning