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

J Surg Res. 2009 Aug;155(2):330-8. doi: 10.1016/j.jss.2008.07.027. Epub 2008 Aug 27.

Abstract

Background: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / pathology*
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Cell Movement / drug effects
  • Disease Models, Animal
  • Estradiol / pharmacology
  • Estradiol / therapeutic use*
  • Female
  • Humans
  • Infusions, Intra-Arterial
  • Macrophages / drug effects
  • Macrophages / pathology
  • Male
  • Orchiectomy
  • Ovariectomy
  • Pancreatic Elastase / administration & dosage
  • Pancreatic Elastase / adverse effects
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / pharmacology
  • Testosterone / therapeutic use*

Substances

  • Testosterone
  • Estradiol
  • Pancreatic Elastase