title: Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.
abstract: OBJECTIVE
  This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation.
  
  
  METHODS
  Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry.
  
  
  RESULTS
  Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments.
  
  
  CONCLUSIONS
  This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Geng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiumei
authors.initials: J
authors.lastname: Cao
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Chen
authors.forename: Rumin
authors.initials: R
authors.lastname: He
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002122:Calcium Chloride / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D003094:Collagen; D051722:ADAM Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000072197:ADAM10 Protein; C542371:ADAM10 protein, rat; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat; D002122:Calcium Chloride