Summary
17 β-estradiol (E2) protects against atherosclerosis independent of changes in plasma lipoproteins in
a variety of animal models, which is explained by direct effects of E2 on the vascular wall. E2 improves vasomotion by modulation of vasoconstrictor and vasodilator systems through
endothelium-dependent and endothelium-independent mechanisms. E2 affects the remodeling of the vascular wall by inhibiting smooth muscle cell proliferation
and accelerating reendothelialization of injured blood vessels. E2 modulates the vascular inflammatory response by inhibiting cytokine production, cyto-kine-induced
expression of cell adhesion molecules and platelet aggregation/adhesion. This review
focuses on the cellular and molecular mechanisms underlying these vasculoprotective
actions of E2.
E2 can act through nongenomic stimulation of membrane/intracel-lular mediators and/or
the classical genomic pathway of steroidactions, which is dependent on transcription
and protein synthesis.The existence of at least two nuclear estrogen receptor (ER)
sub-types Land 13 and a putative membrane ER present the potentialof tissue-specific
as well as biologically different E2 actions. NuclearERs act as ligand-activated transcription factors and can affectgene
regulation by interaction with the classical estrogen responseelement or other nonreceptor
transcription factors. The molecularbasis of genomic E2 actions by identifying transcription factors andregulatory elements involved in the
induction and inhibition of E2regulated gene expression is only at the beginning of being under-stood. The impact
of E2-mediated increased NO availability on thehemodynamic and antiatherosclerotic actions
of E2 is still a debateof controversy.
Key-Word
17 β-estradiol - Vascular wall - Estrogen receptor - Transcription factors - Nitric
oxide
