title: Elastic fiber regeneration in vitro and in vivo for treatment of experimental abdominal aortic aneurysm.
abstract: BACKGROUND
  The pathological characteristics of abdominal aortic aneurysm (AAA) involved the regression of extracellular matrix (ECM) in aortic walls, especially elastic structure in medial layer. As the major structural protein of aorta, elastin contributes to the extensibility and elastic recoil of the vessels. We hypothesized that overexpression of elastin in vessel walls might regenerate the elastic structure of ECM, restore the elastic structure of the aneurysmal wall, and eventually lead to a reduction of aortic diameters (ADs) in an experimental model of AAA.
  
  
  METHODS
  Tropoelastin (TE) of Sprague Dawley (SD) rat was synthesized by reverse transcription polymerase chain reaction and used to construct adneviral vectors containing elastin precursor protein (AdTE-GFP). Cultured vascular smooth muscle cells (VSMCs) from aortas of male SD rats were transfected with AdTE-GFP, AdGFP, adenoviral vector (AdNull), and phosphate buffered saline (PBS). Immunofluorescence staining was performed to determine the expression of elastin in transfected cells. The expression of elastic fibers in ECM of VSMCs transfected with AdTE-GFP were detected by fluorescence microscopy and transmission electron microscopy (TEM) at 1, 3, and 5 days following gene transfer. The AAA vessel walls were infused with AdTE-GFP or an empty AdNull, or PBS directly into the aneurysmal lumen. ADs of the aneurysms were compared in infused aortas. Formation of new elastic fibers in vivo was assessed by hematoxylin and eosin, and elastic von-Giesson staining. Recombinant elastin-GFP in vivo was identified by immunohistochemical staining.
  
  
  RESULTS
  Elastic fibers were increased both in ECM of VSMC and in vessel walls after gene transfer. Histological studies revealed that the AdTE-GFP-transduced aortas had elastic fiber regeneration in the aneurysmal walls. The AdTE-GFP-transduced aortas showed a decreased AD (23.04% ± 14.49%, P < 0.01) in AAA vessel walls.
  
  
  CONCLUSIONS
  Elastic fibers have been successfully overexpressed both in vitro and in a rat model of AAA by a technique of gene transfer. The overexpression of elastic fibers within the aneurysmal tissue appeared to reverse the aneurysm dilatation in this model.
authors: Department of Vascular and Endovascular Surgery, Vascular Surgery Center of People's Liberation Army, Chinese People's Liberation Army General Hospital, Beijing 100853, China. xiongjiangdoc@126.com
authors: Jiang
authors: J
authors: Xiong
authors: Wei
authors: W
authors: Guo
authors: Ren
authors: R
authors: Wei
authors: Shang-wei
authors: SW
authors: Zuo
authors: Xiao-ping
authors: XP
authors: Liu
authors: Tao
authors: T
authors: Zhang
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000628:therapy*; D004547:Elastic Tissue / Q000378:metabolism*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism
chemical_list: D014333:Tropoelastin; D004549:Elastin