{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:34:38Z","timestamp":1787852078301,"version":"build-2784847793"},"reference-count":207,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1R21AG065923"],"award-info":[{"award-number":["1R21AG065923"]}]},{"name":"National Institutes of Health","award":["1R01HL147095"],"award-info":[{"award-number":["1R01HL147095"]}]},{"name":"National Institutes of Health","award":["1R01HL167511"],"award-info":[{"award-number":["1R01HL167511"]}]},{"name":"National Institutes of Health","award":["5R01DK124408"],"award-info":[{"award-number":["5R01DK124408"]}]},{"name":"rohn\u2019s and Colitis Foundation of America\u2014Litwin IBD Pioneers Award (MSL)","award":["1R21AG065923"],"award-info":[{"award-number":["1R21AG065923"]}]},{"name":"rohn\u2019s and Colitis Foundation of America\u2014Litwin IBD Pioneers Award (MSL)","award":["1R01HL147095"],"award-info":[{"award-number":["1R01HL147095"]}]},{"name":"rohn\u2019s and Colitis Foundation of America\u2014Litwin IBD Pioneers Award (MSL)","award":["1R01HL167511"],"award-info":[{"award-number":["1R01HL167511"]}]},{"name":"rohn\u2019s and Colitis Foundation of America\u2014Litwin IBD Pioneers Award (MSL)","award":["5R01DK124408"],"award-info":[{"award-number":["5R01DK124408"]}]},{"name":"Foundation for Anesthesia Education and Research (JC)","award":["1R21AG065923"],"award-info":[{"award-number":["1R21AG065923"]}]},{"name":"Foundation for Anesthesia Education and Research (JC)","award":["1R01HL147095"],"award-info":[{"award-number":["1R01HL147095"]}]},{"name":"Foundation for Anesthesia Education and Research (JC)","award":["1R01HL167511"],"award-info":[{"award-number":["1R01HL167511"]}]},{"name":"Foundation for Anesthesia Education and Research (JC)","award":["5R01DK124408"],"award-info":[{"award-number":["5R01DK124408"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microvascular ischemia, especially in the heart and kidneys, is associated with inflammation and metabolic perturbation, resulting in cellular dysfunction and end-organ failure. Heightened production of adenosine from extracellular nucleotides released in response to inflammation results in protective effects, inclusive of adaptations to hypoxia, endothelial cell nitric oxide release with the regulation of vascular tone, and inhibition of platelet aggregation. Purinergic signaling is modulated by ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)\/CD39, which is the dominant factor dictating vascular metabolism of extracellular ATP to adenosine throughout the cardiovascular tissues. Excess levels of extracellular purine metabolites, however, have been associated with metabolic and cardiovascular diseases. Physiological estrogen signaling is anti-inflammatory with vascular protective effects, but pharmacological replacement use in transgender and postmenopausal individuals is associated with thrombosis and other side effects. Crucially, the loss of this important sex hormone following menopause or with gender reassignment is associated with worsened pro-inflammatory states linked to increased oxidative stress, myocardial fibrosis, and, ultimately, diastolic dysfunction, also known as Yentl syndrome. While there is a growing body of knowledge on distinctive purinergic or estrogen signaling and endothelial health, much less is known about the relationships between the two signaling pathways. Continued studies of the interactions between these pathways will allow further insight into future therapeutic targets to improve the cardiovascular health of aging women without imparting deleterious side effects.<\/jats:p>","DOI":"10.3390\/ijms26052105","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T08:04:44Z","timestamp":1740643484000},"page":"2105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of Estrogen on Purinergic Signaling in Microvascular Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5902-2552","authenticated-orcid":false,"given":"Jessica","family":"Cassavaugh","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-1249","authenticated-orcid":false,"given":"Maria Serena","family":"Longhi","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-0194","authenticated-orcid":false,"given":"Simon C.","family":"Robson","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1016\/j.jacc.2018.09.042","article-title":"Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review","volume":"72","author":"Taqueti","year":"2018","journal-title":"J. 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