Response to sex hormones differs in atherosclerosis-susceptible and -resistant mice

Mylène Potier, Michael Karl, Sharon J. Elliot, Gary E. Striker, Liliane J. Striker

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Genetic factors that determine the degree of susceptibility to atherosclerosis may also influence the effects of estrogens and progestins in arterial vessel disease. We examined and compared estrogen receptor (ER) and progesterone receptor (PR) expression and the effects of 17β-estradiol (E2) and progesterone (P) on collagen synthesis and matrix metalloproteinase (MMP) activities in the aortic arch and in cultured aortic smooth muscle cells (ASMC) of atherosclerosis-susceptible (C57Bl6/J, B6) or -resistant (C3H/HeJ, C3H) mice. ERα, ERβ, and PR levels were higher in the aorta and ASMC of atherosclerosis-susceptible B6 mice. In transfection studies using an estrogen response element-driven reporter plasmid, E 2 elicited a >2-fold increase in luciferase activity in ASMC of B6 (B6-ASMC), which demonstrated the transcriptional activity of ER in atherosclerosis-susceptible cells. Importantly, the response of endogenous target genes to E2 and P was different in B6-ASMC and C3H-ASMC. E2 decreased collagen synthesis but had no effect on MMP activities in B6-ASMC. P decreased MMP-2 and MMP-9 activity in B6-ASMC. In contrast, E 2 increased MMP-2 and decreased MMP-9 activity but had no effect on collagen synthesis in C3H-ASMC. P had no effect on collagen synthesis and MMP activity in C3H-ASMC. These differences in response to sex hormones may have important implications for women who receive hormone replacement therapy.

Original languageEnglish (US)
Pages (from-to)E1237-E1245
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number6 48-6
StatePublished - Dec 1 2003

    Fingerprint

Keywords

  • Collagen
  • Estrogen receptor
  • Matrix metalloproteinase
  • Progesterone receptor
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this