Gender differences in experimental aortic aneurysm formation.
OBJECTIVE
It is hypothesized that a male predominance, similar to that in humans, persists in a rodent model of experimental abdominal aortic aneurysm (AAA) via alterations in matrix metalloproteinases (MMPs).


RESULTS
Group I experiments were as follows: elastase perfusion of the infrarenal aorta was performed in male (M) and female (F) rats. At 14 days, aortas were harvested for immunohistochemistry, real-time polymerase chain reaction (PCR), and zymography. Group II experiments were the following: abdominal aorta was transplanted from F or M donors into F or M recipients. At 14 days, rodents that had undergone transplantation underwent elastase perfusion. In group III, male rats were given estradiol or sham 5 days before elastase perfusion. In group I, M rats had larger AAAs with higher frequency than did F rats. M rat aortas had more significant macrophage infiltrates and increased matrix metalloproteinase (MMP)-9 production and activity. In group II, M-to-M aortic transplants uniformly developed aneurysms after elastase perfusion, whereas F-to-F aortic transplants remained resistant to aneurysm formation. F aortas transplanted into M recipients, however, lost aneurysm resistance. In group III, estradiol-treated rats demonstrated smaller aneurysms and less macrophage infiltrate and MMP-9 compared with M controls after elastase.


CONCLUSIONS
These data provide evidence of gender-related differences in AAA development, which may reflect an estrogen-mediated reduction in macrophage MMP-9 production.
Ailawadi
Gorav
G
Jobst Vascular Research Laboratories, University of Michigan Medical School, Ann Arbor, USA.
Eliason
Jonathan L
JL
Roelofs
Karen J
KJ
Sinha
Indranil
I
Hannawa
Kevin K
KK
Kaldjian
Eric P
EP
Lu
Guanyi
G
Henke
Peter K
PK
Stanley
James C
JC
Weiss
Stephen J
SJ
Thompson
Robert W
RW
Upchurch
Gilbert R
GR
D000818:Animals; D001011:Aorta; D001012:Aorta, Abdominal / Q000378:metabolism / Q000637:transplantation; D017544:Aortic Aneurysm, Abdominal / Q000276:immunology / Q000473:pathology*; D004343:Drug Implants; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D010196:Pancreatic Elastase / Q000494:pharmacology; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014184:Transplantation, Homologous
D004343:Drug Implants; D004967:Estrogens; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9