Emerging evidence of the importance of rapid, non-nuclear estrogen receptor signaling in the cardiovascular system

[Display omitted] ► Emerging evidence supports an important role of rapid ER signaling in the cardiovascular system. ► In vascular endothelial cells, the rapid signaling accelerates cell migration and proliferation. ► In vascular smooth muscle cells, the rapid signaling inhibits cell proliferation. ► The rapid signaling pathway does not effect the growth of breast cancer and endometrial tissue. Estrogen receptors are classically known as ligand-activated transcription factors that regulate gene transcription in cells in response to hormone binding. In addition to this “genomic” signaling pathway, a “rapid, non-nuclear” signaling pathway mediated by cell membrane-associated estrogen receptors also has been recognized. Although for many years there was little evidence to support any physiological relevance of rapid-signaling, very recently evidence has been accumulating supporting the importance of the rapid, non-nuclear signaling as potentially critical for the protective effects of estrogen in the cardiovascular system. Better understanding of the rapid, non-nuclear signaling potentially provides an opportunity to design “pathway-specific” selective estrogen receptor modulators capable of differentially regulating non-nuclear vs. genomic effects that may prove useful ultimately as specific therapies for cardiovascular diseases.