Enhancing Endothelial Progenitor Cell Function Through Selective Estrogen Receptor Modulation: A Potential Approach to Cardiovascular Risk Reduction

Abstract

Estrogen receptors (ER) have been targets of pharmacological intervention for decades. The use of menopausal hormone therapy (MHT) for improving cardiovascular health is associated with serious adverse effects and therefore cannot be recommended as a first-line strategy. While recently menopausal women in good cardiovascular health may be more likely to benefit from MHT than older women with worse risk profiles, adverse MHT effects such as increased risk for stroke have been consistently shown. Selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have been developed to avoid such negative aspects of MHT. Based on available evidence, however, SERMs are not endowed with greater cardiovascular efficacy and safety than conventional MHT. By contrast, the newly developed SERM lasofoxifene has been shown to reduce cardiovascular events in post-menopausal women, although it also increased venous thromboembolic events in line with other ER-targeting agents. Fundamental research has shown that endothelial progenitor cells are important targets of estrogen actions in the cardiovascular system. This indicates that preferential targeting of specific cells and tissues is likely to enhance safety over nonselective hormone agents. Similarly, increased ER-isoform selectivity along with deeper understanding of ER biology should assist in designing novel ER modulators that are more effective and safer than currently used agents. In this article, we summarize the potential connections between SERMs and EPC biology, uncovering novel possible routes to cardiovascular risk reduction.

Evaluation of BMMSCs-EPCs sheets for repairing alveolar bone defects in ovariectomized rats

“…Mobilizing endogenous EPCs from bone marrow may be a feasible method that can not only increase the generation of new blood vessels but also be used to treat ischemic cardiovascular disease. Pro-inflammatory cytokines, growth factors, cytokines, and hormones can mobilize EPCs 16 – 18 , and EPCs can improve the function and activity of BMMSCs in vitro . BMMSCs have good proliferation and differentiation capacity under the appropriate experimental conditions in vitro .…”

Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia

“…The endothelial progenitor cells (EPCs) play a crucial role in repairing the injured endothelium and re-endothelialization [ 14 ]. The amount and bioactivity of endothelial progenitor cells have became an important indicator of vascular endothelial function and risk assessment in cardiovascular disease [ 15 , 16 ]. What’s the effect of elevated nitrative stress on endothelial progenitor cells in hyperhomocysteinemia?…”

Estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor

“…It is also becoming increasingly clear that the ability of EPCs to migrate and form colonies ex vivo is an independent marker of vascular health [4], but it is not clear whether gender influences this phenomenon, although ex vivo experiments show that the function of EPCs (in terms of migratory capacity and colony formation) seems to be higher in women than in men [4,5,6]. Furthermore, EPCs are a fundamental target of estrogen actions in the cardiovascular system [7], and their proliferation, senescence and adhesion seem to be regulated via estrogen receptor (ERs) pathways [6,8]. However, the effect of xenobiotic estrogenic compounds such as bisphenol A (BPA) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC) on human EPCs is unknown.…”