title: N-(2-Aminoethyl) Ethanolamine-Induced Morphological, Biochemical, and Biophysical Alterations in Vascular Matrix Associated With Dissecting Aortic Aneurysm.
abstract: Dissecting aortic aneurysm (DAA) is an extended tear in the wall of the aorta along the plane of the vascular media. Our previous studies indicated in a developmental animal model, that DAA was related to pathological alteration in collagen, especially collagen type III. Accordingly, in the present studies, neonatal aortic vascular smooth muscle cells (VSMC) and timed pregnant Sprague-Dawley rat dams were treated with N-(2-aminoethyl) ethanolamine (AEEA), which, as shown previously, causes DAA in offspring. Morphological changes in extracellular matrix (ECM) produced by VSMC in vitro were detailed with scanning electron microscopy (SEM), and biochemical changes in cells and ECM produced by VSMCs were defined by Western blotting. Biophysical changes of the collagen extracted from both the ECM produced by VSMC and extracted from fetal rat aortas were studied with atomic force microscopy (AFM). ECM disruption and irregularities were observed in VSMCs treated with AEEA by SEM. Western blotting showed that collagen type I was much more extractable, accompanied by a decrease of the pellet size after urea buffer extraction in the AEEA-treated VSMC when compared with the control. AFM found that collagen samples extracted from the fetal rat aortas of the AEEA-treated dam, and in the in vitro formed ECM prepared by decellularization, became stiffer, or more brittle, indicating that the 3D organization associated with elasticity was altered by AEEA exposure. Our results show that AEEA causes significant morphological, biochemical, and biomechanical alterations in the ECM. These in vitro and in vivo strategies are advantageous in elucidating the underlying mechanisms of DAA.
authors.affiliation: Department of Pathology;
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology;
authors.forename: Ya
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neuroscience and Cell Biology; and.
authors.forename: Paul
authors.initials: P
authors.lastname: Bujalowski
authors.affiliation: Department of Neuroscience and Cell Biology; and Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555.
authors.forename: Andres F
authors.initials: AF
authors.lastname: Oberhauser
authors.affiliation: Department of Pathology; pboor@utmb.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Boor
mesh_terms: D000784:Aortic Dissection / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D004983:Ethanolamines / Q000633:toxicity*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D004983:Ethanolamines; C035835:N-(2-hydroxyethyl)ethylenediamine
keywords: N-(2-aminoethyl) ethanolamine (AEEA); aorta; collagen; dissecting aortic aneurysm (DAA); vascular extracellular matrix (ECM); vascular smooth muscle cells (VSMCs)