title: Interference of doxycycline pretreatment in a model of abdominal aortic aneurysms.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) is characterized by chronic inflammation and degradation of the extracellular matrix, mediated by matrix metalloproteinases (MMPs). Doxycycline has been reported to control the progression of AAA by regulation of MMP. We hypothesized that doxycycline pretreatment in a rat model of AAA would cause reduction in gelatinolytic activity of MMP-2 and -9 and the inflammatory response in the wall of an aneurysm, consequently decreasing the formation and development of AAAs.
  
  
  METHODS
  Male Wistar rats were divided into the following four groups: aneurysm (A); control (C); aneurysm+doxycycline (A+D) and control+doxycycline (C+D), with 24 animals per group subdivided into n=6 animals at different time points [1, 3, 7, and 15 days postsurgery (dps)]. The (A) and (A+D) groups simultaneously received the injury and extrinsic stenosis of the aortic wall. The (C) and (C+D) groups received sham operation. The treated animals received doxycycline via gavage (30 mg/kg/day) from 48 h before surgery until the end of experiment. At 1, 3, 7, and 15 dps, the animals were euthanized, and the aortas were collected for morphological analyses, immunohistochemistry, and zymography.
  
  
  RESULTS
  The animals from the (A) group developed AAAs. However, the animals treated with doxycycline showed a 85% decrease in AAA development, which was associated with a large reduction in gelatinolytic activity of MMP-2 and -9, and decreased inflammatory response (P<.05).
  
  
  CONCLUSIONS
  These results suggest that pretreatment with doxycycline before surgery inhibited the activity of MMP-2 and -9, as well as the inflammatory response, and may play an important role in the prevention of the development of AAAs.
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Karina M
authors.initials: KM
authors.lastname: Mata
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Tefé-Silva
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Floriano
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Cleverson R
authors.initials: CR
authors.lastname: Fernandes
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Elen
authors.initials: E
authors.lastname: Rizzi
authors.affiliation: Department of Morphology and Physiology, Dental School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Gerlach
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Marc Q
authors.initials: MQ
authors.lastname: Mazzuca
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. Electronic address: sgramos@fmrp.usp.br.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Ramos
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology / Q000473:pathology*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline
keywords: Abdominal aortic aneurysm; Doxycycline pretreatment; Inflammatory response; Metalloproteinases 2 and 9