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

Prossnitz, 2015, International Union of Basic and Clinical Pharmacology. XCVII. G protein-coupled estrogen receptor and its pharmacologic modulators, Pharmacol. Rev., 67, 505, 10.1124/pr.114.009712

Pare, 2002, Estrogen receptor-α mediates the protective effects of estrogen against vascular injury, Circ. Res., 90, 1087, 10.1161/01.RES.0000021114.92282.FA

Bolego, 2010, Selective estrogen receptor-α agonist provides widespread heart and vascular protection with enhanced endothelial progenitor cell mobilization in the absence of uterotrophic action, FASEB J., 24, 2262, 10.1096/fj.09-139220

Marcantoni, 2012, Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression, Prostaglandins Other Lipid Mediat., 98, 122, 10.1016/j.prostaglandins.2012.01.006

Murphy, A.J., Guyre, P.M., Wira, C.R., and Pioli, P.A. (2009). Estradiol regulates expression of estrogen receptor ERα46 in human macrophages. PLoS ONE, 4.

Geraldes, 2002, Estrogen regulation of endothelial and smooth muscle cell migration and proliferation: Role of p38 and p42/44 mitogen-activated protein kinase, Arterioscler. Thromb. Vasc. Biol., 22, 1585, 10.1161/01.ATV.0000035393.11854.6A

Maggi, 2003, Diabetes undermines estrogen control of inducible nitric oxide synthase function in rat aortic smooth muscle cells through overexpression of estrogen receptor-β, Circulation, 108, 211, 10.1161/01.CIR.0000079311.39939.94

Morales, 1995, Estrogen promotes angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model, Circulation, 91, 755, 10.1161/01.CIR.91.3.755

Concina, 2000, The mitogenic effect of 17β-estradiol on in vitro endothelial cell proliferation and on in vivo reendothelialization are both dependent on vascular endothelial growth factor, J. Vasc. Res., 37, 202, 10.1159/000025732

Simoncini, 2006, Estrogen receptor α interacts with Gα13 to drive actin remodeling and endothelial cell migration via the RhoA/Rho kinase/moesin pathway, Mol. Endocrinol., 20, 1756, 10.1210/me.2005-0259

Trenti, 2017, The glycolytic enzyme PFKFB3 is involved in estrogen-mediated angiogenesis via GPER1, J. Pharmacol. Exp. Ther., 361, 398, 10.1124/jpet.116.238212

Bao, 2003, Diurnal rhythm of free estradiol during the menstrual cycle, Eur. J. Endocrinol., 148, 227, 10.1530/eje.0.1480227

Wildman, 2008, Associations of endogenous sex hormones with the vasculature in menopausal women: The Study of Women’s health Across the Nation (SWAN), Menopause, 15, 414, 10.1097/gme.0b013e318154b6f5

Clegg, 2013, The role of estrogens in control of energy balance and glucose homeostasis, Endocr. Rev., 34, 309, 10.1210/er.2012-1055

Cignarella, 2010, Emerging role of estrogen in the control of cardiometabolic disease, Trends Pharmacol. Sci., 31, 183, 10.1016/j.tips.2010.01.001

Benedusi, 2014, Energy metabolism and fertility: A balance preserved for female health, Nat. Rev. Endocrinol., 10, 13, 10.1038/nrendo.2013.203

Krasinski, 1997, Estradiol accelerates functional endothelial recovery after arterial injury, Circulation, 95, 1768, 10.1161/01.CIR.95.7.1768

Iwakura, 2003, Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury, Circulation, 108, 3115, 10.1161/01.CIR.0000106906.56972.83

Strehlow, 2003, Estrogen increases bone marrow-derived endothelial progenitor cell production and diminishes neointima formation, Circulation, 107, 3059, 10.1161/01.CIR.0000077911.81151.30

Toutain, 2009, Estrogen receptor α expression in both endothelium and hematopoietic cells is required for the accelerative effect of estradiol on reendothelialization, Arterioscler. Thromb. Vasc. Biol., 29, 1543, 10.1161/ATVBAHA.109.192849

Rubanyi, 2002, Effect of estrogen on endothelial function and angiogenesis, Vasc. Pharmacol., 38, 89, 10.1016/S0306-3623(02)00131-3

Filipe, 2008, Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium, Am. J. Physiol. Heart Circ. Physiol., 294, H2822, 10.1152/ajpheart.00129.2008

Brouchet, 2001, Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-α but not estrogen receptor-β, Circulation, 103, 423, 10.1161/01.CIR.103.3.423

Hardman, 2008, Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly, Genome Biol., 9, R80, 10.1186/gb-2008-9-5-r80

Libert, 2010, The X chromosome in immune functions: When a chromosome makes the difference, Nat. Rev. Immunol., 10, 594, 10.1038/nri2815

2015, Sex, the aging immune system, and chronic disease, Cell. Immunol., 294, 102, 10.1016/j.cellimm.2015.02.002

Amadori, 1995, Genetic control of the CD4/CD8 T-cell ratio in humans, Nat. Med., 1, 1279, 10.1038/nm1295-1279

Scotland, 2011, Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice, Blood, 118, 5918, 10.1182/blood-2011-03-340281

Benedek, 2017, Novel feedback loop between M2 macrophages/microglia and regulatory B cells in estrogen-protected EAE mice, J. Neuroimmunol., 305, 59, 10.1016/j.jneuroim.2016.12.018

Nadkarni, 2013, Oestrogen and immunomodulation: New mechanisms that impact on peripheral and central immunity, Curr. Opin. Pharmacol., 13, 576, 10.1016/j.coph.2013.05.007

Maggi, 2017, Sex differences: A resultant of an evolutionary pressure?, Cell. Metab., 25, 499, 10.1016/j.cmet.2017.01.006

Bolego, 2006, Selective agonists of estrogen receptor isoforms: New perspectives for cardiovascular disease, Arterioscler. Thromb. Vasc. Biol., 26, 2192, 10.1161/01.ATV.0000242186.93243.25

Revankar, 2005, A transmembrane intracellular estrogen receptor mediates rapid cell signaling, Science, 307, 1625, 10.1126/science.1106943

Chakrabarti, S., and Davidge, S.T. (2012). G-protein coupled receptor 30 (GPR30): A novel regulator of endothelial inflammation. PLoS ONE, 7.

Kumar, 2011, The dynamic structure of the estrogen receptor, J. Amino Acids, 2011, 812540, 10.4061/2011/812540

Heldring, 2007, Estrogen receptors: How do they signal and what are their targets, Physiol. Rev., 87, 905, 10.1152/physrev.00026.2006

Leitman, 2010, Regulation of specific target genes and biological responses by estrogen receptor subtype agonists, Curr. Opin. Pharmacol., 10, 629, 10.1016/j.coph.2010.09.009

Kim, 2009, Membrane-initiated actions of estrogen on the endothelium, Mol. Cell. Endocrinol., 308, 3, 10.1016/j.mce.2009.03.025

Acconcia, 2005, Palmitoylation-dependent estrogen receptor α membrane localization: Regulation by 17β-estradiol, Mol. Biol. Cell, 16, 231, 10.1091/mbc.e04-07-0547

Krust, 2011, Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing, Proc. Natl. Acad. Sci. USA, 108, 13311, 10.1073/pnas.1105632108

Adlanmerini, 2014, Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions, Proc. Natl. Acad. Sci. USA, 111, E283, 10.1073/pnas.1322057111

Filardo, 2012, Minireview: G protein-coupled estrogen receptor-1, GPER-1: Its mechanism of action and role in female reproductive cancer, renal and vascular physiology, Endocrinology, 153, 2953, 10.1210/en.2012-1061

Pelekanou, 2016, Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1, J. Leukoc. Biol., 99, 333, 10.1189/jlb.3A0914-430RR

Albanito, 2007, G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17β-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells, Cancer Res., 67, 1859, 10.1158/0008-5472.CAN-06-2909

Gao, 2011, GPR30 activation opposes estrogen-dependent uterine growth via inhibition of stromal ERK1/2 and estrogen receptor alpha (ERα) phosphorylation signals, Endocrinology, 152, 1434, 10.1210/en.2010-1368

Traupe, 2007, Distinct roles of estrogen receptors α and β mediating acute vasodilation of epicardial coronary arteries, Hypertension, 49, 1364, 10.1161/HYPERTENSIONAHA.106.081554

Romano, S.N., and Gorelick, D.A. (2017). Crosstalk between nuclear and G protein-coupled estrogen receptors. Gen. Comp. Endocrinol.

Venkov, 1996, Identification of authentic estrogen receptor in cultured endothelial cells—A potential mechanism for steroid hormone regulation of endothelial function, Circulation, 94, 727, 10.1161/01.CIR.94.4.727

Karas, 1994, Human vascular smooth muscle cells contain functional estrogen receptor, Circulation, 89, 1943, 10.1161/01.CIR.89.5.1943

Simoncini, 2000, Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule-1 expression by different transcriptional mechanisms, Circ. Res., 87, 19, 10.1161/01.RES.87.1.19

Harris, 2002, Characterization of the biological roles of the estrogen receptors, ERα and ERβ, in estrogen target tissues in vivo through the use of an ERα-selective ligand, Endocrinology, 143, 4172, 10.1210/en.2002-220403

Mendelsohn, 2005, Molecular and cellular basis of cardiovascular gender differences, Science, 308, 1583, 10.1126/science.1112062

Ospina, 2002, 17β-estradiol increases rat cerebrovascular prostacyclin synthesis by elevating cyclooxygenase-1 and prostacyclin synthase, Stroke, 33, 600, 10.1161/hs0202.102732

Egan, 2004, COX-2-derived prostacyclin confers atheroprotection on female mice, Science, 306, 1954, 10.1126/science.1103333

Nevzati, 2015, Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells, Acta Neurochir. Suppl., 120, 141, 10.1007/978-3-319-04981-6_24

Papapetropoulos, 1997, Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells, J. Clin. Investig., 100, 3131, 10.1172/JCI119868

Ziche, 1997, Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis, J. Clin. Investig., 99, 2625, 10.1172/JCI119451

Novensa, L., Novella, S., Medina, P., Segarra, G., Castillo, N., Heras, M., Hermenegildo, C., and Dantas, A.P. (2011). Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice. PLoS ONE, 6.

Rowlands, 2011, Equol-stimulated mitochondrial reactive oxygen species activate endothelial nitric oxide synthase and redox signaling in endothelial cells: Roles for F-actin and GPR30, Hypertension, 57, 833, 10.1161/HYPERTENSIONAHA.110.162198

Thomas, 2005, Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells, Endocrinology, 146, 624, 10.1210/en.2004-1064

Meyer, 2016, Obligatory role for GPER in cardiovascular aging and disease, Sci. Signal., 9, ra105, 10.1126/scisignal.aag0240

Reynolds, 1992, Angiogenesis in the female reproductive system, FASEB J., 6, 886, 10.1096/fasebj.6.3.1371260

Alvarez, 1997, 17β-estradiol inhibits apoptosis of endothelial cells, Biochem. Biophys. Res. Commun., 237, 372, 10.1006/bbrc.1997.7085

Spyridopoulos, 1997, Estrogen-receptor-mediated inhibition of human endothelial cell apoptosis. Estradiol as a survival factor, Circulation, 95, 1505, 10.1161/01.CIR.95.6.1505

Sanchez, 2011, Estrogen receptor-α promotes endothelial cell motility through focal adhesion kinase, Mol. Hum. Reprod., 17, 219, 10.1093/molehr/gaq097

Johns, 1996, Disruption of estrogen receptor gene prevents 17 beta estradiol-induced angiogenesis in transgenic mice, Endocrinology, 137, 4511, 10.1210/endo.137.10.8828515

Oviedo, 2007, Raloxifene increases proliferation of human endothelial cells in association with increased gene expression of cyclins A and B1, Fertil. Steril., 88, 326, 10.1016/j.fertnstert.2006.11.185

Oviedo, 2011, Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway, Mol. Cell. Endocrinol., 335, 96, 10.1016/j.mce.2010.06.020

Karas, 1998, Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway, J. Clin. Investig., 101, 2851, 10.1172/JCI1416

Shifren, 1996, Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: Implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis, J. Clin. Endocrinol. Metab., 81, 3112

Gargett, 2002, 17β-estradiol up-regulates vascular endothelial growth factor receptor-2 expression in human myometrial microvascular endothelial cells: Role of estrogen receptor-α and -β, J. Clin. Endocrinol. Metab., 87, 4341, 10.1210/jc.2001-010588

Cid, 1999, Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function, Angiogenesis, 3, 271, 10.1023/A:1009023329294

Haran, 1994, Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth, Cancer Res., 54, 5511

Dadiani, 2009, Estrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: The role of estrogen receptor α and c-Myc, Endocr. Relat. Cancer, 16, 819, 10.1677/ERC-08-0249

Osthus, 2000, Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc, J. Biol. Chem., 275, 21797, 10.1074/jbc.C000023200

Pedram, 2013, Estrogen reduces lipid content in the liver exclusively from membrane receptor signaling, Sci. Signal., 6, ra36, 10.1126/scisignal.2004013

Guillaume, 2017, Nuclear and membrane actions of estrogen receptor alpha: Contribution to the regulation of energy and glucose homeostasis, Adv. Exp. Med. Biol., 1043, 401, 10.1007/978-3-319-70178-3_19

Georgiadou, 2013, Role of PFKFB3-driven glycolysis in vessel sprouting, Cell, 154, 651, 10.1016/j.cell.2013.06.037

Clem, 2014, Estradiol stimulates glucose metabolism via 6-phosphofructo-2-kinase (PFKFB3), J. Biol. Chem., 289, 9440, 10.1074/jbc.M113.529990

De Francesco, E.M., Sotgia, F., Clarke, R.B., Lisanti, M.P., and Maggiolini, M. (2017). G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis: Old paradigms and emerging concepts. Int J. Mol. Sci., 18.

Sica, 2012, Macrophage plasticity and polarization: In vivo veritas, J. Clin. Investig., 122, 787, 10.1172/JCI59643

Mosser, 2008, Exploring the full spectrum of macrophage activation, Nat. Rev. Immunol., 8, 958, 10.1038/nri2448

Mantovani, 2013, Macrophage plasticity and polarization in tissue repair and remodelling, J. Pathol., 229, 176, 10.1002/path.4133

Xue, 2014, Transcriptome-based network analysis reveals a spectrum model of human macrophage activation, Immunity, 40, 274, 10.1016/j.immuni.2014.01.006

Qian, 2010, Macrophage diversity enhances tumor progression and metastasis, Cell, 141, 39, 10.1016/j.cell.2010.03.014

Brecht, 2011, Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E2, FASEB J., 25, 2408, 10.1096/fj.10-179473

Bruemmer, 2012, Targeting angiogenesis as treatment for obesity, Arterioscler. Thromb. Vasc. Biol., 32, 161, 10.1161/ATVBAHA.111.241992

Miller, 2004, Estrogen modulates inflammatory mediator expression and neutrophil chemotaxis in injured arteries, Circulation, 110, 1664, 10.1161/01.CIR.0000142050.19488.C7

Hsieh, 2007, Downregulation of migration inhibitory factor is critical for estrogen-mediated attenuation of lung tissue damage following trauma-hemorrhage, Am. J. Physiol. Lung Cell. Mol. Physiol., 292, L1227, 10.1152/ajplung.00479.2006

Giannoni, 2011, Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns, Infect. Immun., 79, 2690, 10.1128/IAI.00076-11

Campesi, 2012, Oral contraceptives modify DNA methylation and monocyte-derived macrophage function, Biol. Sex. Differ., 3, 4, 10.1186/2042-6410-3-4

Pechenino, 2011, Impact of aging vs. estrogen loss on cardiac gene expression: Estrogen replacement and inflammation, Physiol. Genom., 43, 1065, 10.1152/physiolgenomics.00228.2010

Toniolo, 2015, Alternative activation of human macrophages is rescued by estrogen treatment in vitro and impaired by menopausal status, J. Clin. Endocrinol. Metab., 100, E50, 10.1210/jc.2014-2751

Xing, D., Oparil, S., Yu, H., Gong, K., Feng, W., Black, J., Chen, Y.F., and Nozell, S. (2012). Estrogen modulates NFκB signaling by enhancing IκBα levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-β. PLoS ONE, 7.

Murphy, 2010, Estradiol suppresses NF-κB activation through coordinated regulation of let-7a and miR-125b in primary human macrophages, J. Immunol., 184, 5029, 10.4049/jimmunol.0903463

Lambert, 2004, Estrogen receptor-α deficiency promotes increased TNF-α secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro, J. Leukoc. Biol., 75, 1166, 10.1189/jlb.1103589

Calippe, 2010, 17β-estradiol promotes TLR4-triggered proinflammatory mediator production through direct estrogen receptor α signaling in macrophages in vivo, J. Immunol., 185, 1169, 10.4049/jimmunol.0902383

Straub, 2007, The complex role of estrogens in inflammation, Endocr. Rev., 28, 521, 10.1210/er.2007-0001

Murray, 2011, Protective and pathogenic functions of macrophage subsets, Nat. Rev. Immunol., 11, 723, 10.1038/nri3073

Spiller, 2014, The role of macrophage phenotype in vascularization of tissue engineering scaffolds, Biomaterials, 35, 4477, 10.1016/j.biomaterials.2014.02.012

Sindrilaru, 2011, An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice, J. Clin. Investig., 121, 985, 10.1172/JCI44490

Campbell, 2014, Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair, J. Investig. Dermatol., 134, 2447, 10.1038/jid.2014.175

Villa, 2015, Estrogen accelerates the resolution of inflammation in macrophagic cells, Sci. Rep., 5, 15224, 10.1038/srep15224

Tang, 2017, Similarities in the metabolic reprogramming of immune system and endothelium, Front. Immunol., 8, 837, 10.3389/fimmu.2017.00837

Blasko, 2009, Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis, J. Neuroimmunol., 214, 67, 10.1016/j.jneuroim.2009.06.023

Rettew, 2010, GPR30/GPER-1 mediates rapid decreases in TLR4 expression on murine macrophages, Mol. Cell. Endocrinol., 328, 87, 10.1016/j.mce.2010.07.017

Kramer, 2007, 17β-estradiol utilizes the estrogen receptor to regulate CD16 expression in monocytes, Mol. Cell. Endocrinol., 279, 16, 10.1016/j.mce.2007.08.014

Campesi, 2017, Sex differences in estrogen receptor α and β levels and activation status in LPS-stimulated human macrophages, J. Cell. Physiol., 232, 340, 10.1002/jcp.25425

Pepe, 2017, Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge, Sci. Rep., 7, 44270, 10.1038/srep44270

Ribas, 2011, Myeloid-specific estrogen receptor α deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development, Proc. Natl. Acad. Sci. USA, 108, 16457, 10.1073/pnas.1104533108

Mitro, 2016, An essential role for liver ERα in coupling hepatic metabolism to the reproductive cycle, Cell Rep., 15, 360, 10.1016/j.celrep.2016.03.019

Bowling, 2014, Estrogen effects on vascular inflammation are age dependent: Role of estrogen receptors, Arterioscler. Thromb. Vasc. Biol.., 34, 1477, 10.1161/ATVBAHA.114.303629

Palmer, 2015, The sexual dimorphism of obesity, Mol. Cell. Endocrinol., 402, 113, 10.1016/j.mce.2014.11.029

Manson, 2017, Menopausal hormone therapy and long-term all-cause and cause-specific mortality: The Women’s Health Initiative randomized trials, JAMA, 318, 927, 10.1001/jama.2017.11217

Schierbeck, 2012, Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: Randomised trial, BMJ, 345, e6409, 10.1136/bmj.e6409

Waligora, 2006, Effect of estrogen/progesterone hormone replacement therapy on natural killer cell cytotoxicity and immunoregulatory cytokine release by peripheral blood mononuclear cells of postmenopausal women, J. Reprod. Immunol., 69, 65, 10.1016/j.jri.2005.07.006

Corcoran, 2010, Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women, J. Endocrinol., 206, 217, 10.1677/JOE-10-0057

Campesi, 2013, Regular cigarette smoking influences the transsulfuration pathway, endothelial function, and inflammation biomarkers in a sex-gender specific manner in healthy young humans, Am. J. Transl. Res., 5, 497