Estrogen is a modulator of vascular inflammation

IUBMB Life. 2008 Jun;60(6):376-82. doi: 10.1002/iub.48.

Abstract

Vascular inflammation underlies the pathogenesis of atherosclerosis. Atherosclerotic changes in the vasculature lead to conditions such as coronary artery disease and stroke, which are the major causes of morbidity and mortality worldwide. Epidemiological studies in premenopausal women suggest a beneficial role for estrogen in preventing vascular inflammation and consequent atherosclerosis. However, the benefits of estrogen areabsent or even reversed in older postmenopausal subjects. The modulation of inflammation by estrogen under different conditions might explain this discrepancy. Estrogen exerts its antiinflammatory effects on the vasculature through different mechanisms such as direct antioxidant effect, generation of nitric oxide, prevention of apoptosis in vascular cells and suppression of cytokines and the renin-angiotensin system. On the other hand, estrogen also elicits proinflammatory changes under certain conditions, which are less completely understood. Some of the mechanisms underlying a possible proinflammatory role for estrogen include increased expression of the proinflammatory receptor for advanced glycation end products, increased tyrosine nitration of cellular proteins, and generation of reactive oxygen species through an uncoupled eNOS. In this review, we have presented evidence for both antiinflammatory and proinflammatory pathways modulated by estrogen and how interactions among such pathways might determine the effects of estrogen on the vascular system.

Publication types

  • Review

MeSH terms

  • Aging
  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Cytokines / metabolism
  • Endothelin-1 / metabolism
  • Estrogens / metabolism*
  • Female
  • Humans
  • Inflammation*
  • Models, Biological
  • Nitric Oxide / metabolism
  • Permeability
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Cytokines
  • Endothelin-1
  • Estrogens
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide