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Differential regulation of aortic growth in male and female rodents is associated with AAA development.

AbstractBACKGROUND:
The objective was to examine effects of gonadal hormone manipulation on aortic diameter and macrophage infiltration in rodents during abdominal aortic aneurysm (AAA) formation.
METHODS:
Experiment 1: 17-beta estradiol and testosterone pellets were implanted in male (ME) and female (FT) rats. No pellet was implanted in shams (MES, FTS). Experiment 2: Testes and ovaries were removed from males (MO) and females (FO), respectively. No organs were removed from shams (MOS, FOS). Experiment 3: Male and female rats were orchiectomized and oophorectomized, respectively. Four weeks post-castration, testosterone (MOT) and 17-beta estradiol (FOE) pellets were implanted. Shams underwent castration, but no pellet was implanted (MOTS, FOES). All rats underwent infrarenal aortic infusion with elastase postimplantation/postcastration. Diameters were measured on postoperative d 14. Tissue was stained for macrophages by immunohistochemistry.
RESULTS:
Diameter (P = 0.046) and macrophage counts (P = 0.014) decreased in ME compared with shams, but not in females treated with testosterone (FT). Diameter (P = 0.019) and macrophage infiltration (P = 0.024) decreased in MO compared with shams, but not in FO. Diameter increased in MOT compared with MOTS (P = 0.033), but decreased in FOE compared with FOES (P = 0.002). Macrophages decreased in FOE compared with FOES (P = 0.002).
CONCLUSION:
This study documents a decrease in AAA diameter in males treated with estrogen or undergoing orchiectomy, but no changes in females treated with testosterone or undergoing oophorectomy; and an increase in diameter in MOT and a decrease in FOE. These data suggest that gonadal hormones differentially regulate AAA growth in association with changes in macrophages.
AuthorsBrenda S Cho, Derek T Woodrum, Karen J Roelofs, James C Stanley, Peter K Henke, Gilbert R Upchurch Jr
JournalThe Journal of surgical research (J Surg Res) Vol. 155 Issue 2 Pg. 330-8 (Aug 2009) ISSN: 1095-8673 [Electronic] United States
PMID19111327 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Testosterone
  • Estradiol
  • Pancreatic Elastase
Topics
  • Animals
  • Aorta, Abdominal (drug effects, pathology)
  • Aortic Aneurysm, Abdominal (chemically induced, pathology, prevention & control)
  • Cell Movement (drug effects)
  • Disease Models, Animal
  • Estradiol (pharmacology, therapeutic use)
  • Female
  • Humans
  • Infusions, Intra-Arterial
  • Macrophages (drug effects, pathology)
  • Male
  • Orchiectomy
  • Ovariectomy
  • Pancreatic Elastase (administration & dosage, adverse effects)
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone (pharmacology, therapeutic use)

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