Decreased collagen and increased matrix metalloproteinase-13 in experimental abdominal aortic aneurysms in males compared with females.
BACKGROUND
This study examined differences in sex in collagen regulation during rodent experimental abdominal aortic aneurysm formation.


METHODS
Infrarenal aortas of male and female rats were perfused with elastase or saline (control). Aortic diameters were measured at baseline (day 0) and on postoperative days 7 and 14. Transforming growth factor-beta 1, collagen subtypes I and III, and matrix metalloproteinase-13 (MMP-13; collagenase-3) expression and/or protein levels from aortic tissue were determined by real-time reverse transcription polymerase chain reaction and Western blotting. Aortic tissue was stained for total collagen, neutrophils, and macrophages using immunohistochemistry on days 4 and 7.


RESULTS
At 7 and 14 days after perfusion, aortic diameter increased in elastase-perfused males compared with females (P < .001 for each). At 4 and 7 days postperfusion, significantly more neutrophils and macrophages were present in elastase-perfused males compared with females. By 7 days postperfusion, protein levels of transforming growth factor-beta 1 were less in males compared with females (P = .04). Type I collagen levels also decreased on days 7 (P < .001) and 14 (P = .002), and type III collagen levels decreased on days 7 (P < .001) and 14 (P < .001) in males compared with females. With Masson's trichrome stain, less adventitial collagen was observed in the elastase-perfused males compared with females. MMP-13 expression (P < .001) and protein levels (P = .006) in elastase-perfused males were greater than females on day 14.


CONCLUSIONS
This study documents a decrease in types I and III collagen with a concurrent increase in MMP-13 after elastase perfusion in males compared with females. These data suggest that alterations in extracellular matrix collagen turnover may be responsible for altered abdominal aortic aneurysm formation between sexes.
Cho
Brenda S
BS
Conrad Jobst Vascular Surgery Research Laboratories, Section of Vascular Surgery, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Roelofs
Karen J
KJ
Ford
John W
JW
Henke
Peter K
PK
Upchurch
Gilbert R
GR
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D009504:Neutrophils / Q000473:pathology; D010196:Pancreatic Elastase / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D053773:Transforming Growth Factor beta1; D010196:Pancreatic Elastase; D053509:Matrix Metalloproteinase 13