Functional importance of connective tissue repair during the development of experimental abdominal aortic aneurysms.

  • Huffman M
  • Curci J
  • Moore G
 et al. 
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Abstract

BACKGROUND: Abdominal aortic aneurysms (AAAs) involve an unfavorable balance between the destruction and the repair of connective tissue proteins. The purpose of this study was to assess the functional importance of connective tissue repair during experimental aneurysmal degeneration.

METHODS: Male Wistar rats (n = 70) underwent transient intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase. In Study I, the aortic diameter was measured before elastase perfusion and at days 0, 2, 7, and 14 (n = 6 rats at each interval). Aortic wall concentrations of desmosine (Des) and hydroxyproline (OHP) were measured at each interval, and the expression of tropoelastin (TE), alpha1(I) procollagen (PC), and lysyl oxidase genes was evaluated by reverse transcription-polymerase chain reaction. In Study II, 22 rats were treated with beta-aminopropionitrile (BAPN) to block connective tissue repair. In Study III (n = 30), rats were treated with doxycycline, a matrix metalloproteinase inhibitor, beginning 7 days after elastase perfusion.

RESULTS: AAAs consistently developed between 7 and 14 days after elastase perfusion. Aortic wall Des concentration decreased markedly during aneurysm development, reaching 3% of normal by day 14 (377 +/- 22 pmol of Des/sample on day 0 vs 9 +/- 1 pmol of Des/sample on day 14; P
CONCLUSIONS: The development of elastase-induced AAAs is accompanied by an active process of connective tissue repair. While this reparative process is necessary to stabilize the developing aneurysm wall, it is insufficient to prevent aneurysm progression. In contrast, reducing the proteolytic destruction of connective tissue proteins promotes stabilization of the aneurysmal aorta.

Author-supplied keywords

  • Aminopropionitrile
  • Aminopropionitrile: pharmacology
  • Animals
  • Aorta, Abdominal
  • Aorta, Abdominal: drug effects
  • Aorta, Abdominal: physiology
  • Aorta, Abdominal: physiopathology
  • Aortic Aneurysm, Abdominal
  • Aortic Aneurysm, Abdominal: chemically induced
  • Aortic Aneurysm, Abdominal: physiopathology
  • Connective Tissue
  • Connective Tissue: drug effects
  • Connective Tissue: physiopathology
  • Desmosine
  • Desmosine: analysis
  • Hydroxyproline
  • Hydroxyproline: analysis
  • Male
  • Pancreatic Elastase
  • Procollagen
  • Procollagen: genetics
  • Protein-Lysine 6-Oxidase
  • Protein-Lysine 6-Oxidase: genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Tropoelastin
  • Tropoelastin: genetics
  • Wound Healing
  • Wound Healing: drug effects

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Authors

  • M D Huffman

  • J A Curci

  • G Moore

  • D B Kerns

  • B C Starcher

  • R W Thompson

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