Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle

Abstract

Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17β-estradiol can influence the cardiovascular and immune systems.

Keywords: 17β-estradiol; angiogenesis; endothelium; estrogen; immune response; macrophages; metabolism.

Figure 1

Multiple effects of 17β-estradiol (E2) in endothelial cells and macrophages. E2 induces protective effects on the cardiovascular system by promoting endothelial healing and angiogenesis through various pathways including the acceleration of re-endothelialization in vivo, the induction of proliferation and rearrangements of the actin cytoskeleton. E2 regulates the induction of chemokines and cytokines, and modulates macrophage immune phenotypes. These events are mediated by intracellular and membrane ER subtypes that are operatively linked in several cell types. The interaction between endothelial cells and macrophages is relevant in multiple disease settings such as atherosclerosis and cancer.