{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:47:10Z","timestamp":1791636430666,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Clinical demographics have demonstrated that postmenopausal women are predisposed to chronic stress-induced cardiomyopathy (CSC) and this has been associated with the decrease of estrogen. Meanwhile, recent studies have implicated unsolved myocardial proinflammatory responses, which are characterized by enormous CD86+ macrophage infiltrations as an underlying disease mechanism expediting the pathological remodeling of the heart during chronic stress. However, we had previously demonstrated that estrogen confers cardioprotection <jats:italic>via<\/jats:italic> the modulation of cardiomyocytes \u03b2<jats:sub>2<\/jats:sub>-adrenoceptors (\u03b2<jats:sub>2<\/jats:sub>AR)-Gs\/Gi pathways during stress to lessen the incidence of stress-induced cardiovascular diseases in premenopausal women. Intriguingly, macrophages express \u03b2<jats:sub>2<\/jats:sub>AR profoundly as well; as such, we sought to elucidate the possibilities of estrogen modulating \u03b2<jats:sub>2<\/jats:sub>AR-Gs\/Gi pathway to confer cardioprotection during stress <jats:italic>via<\/jats:italic> immunomodulation. To do this, ovariectomy (OVX) and sham operations (Sham) were performed on female Sprague-Dawley (SD) rats. Two weeks after OVX, the rats were injected with 40 \u03bcg\/kg\/day of estradiol (E<jats:sub>2<\/jats:sub>). Next, on day 36 after OVX, chronic stress was induced by a daily subcutaneous injection of 5 mg\/kg\/day of isoproterenol (ISO). The effect of E<jats:sub>2<\/jats:sub> on relevant clinical cardiac function indexes (LVSP, LVEDP, + dp\/dt and \u2212dp\/dt), myocardial architecture (cardiomyocyte diameter and fibrosis), \u03b2<jats:sub>2<\/jats:sub>AR alterations, and macrophage (CD86+ and CD206+) infiltrations were assessed. <jats:italic>In vitro<\/jats:italic>, peritoneal macrophages (PM<jats:sub>\u03a6<\/jats:sub>) were isolated from wild-type and \u03b2<jats:sub>2<\/jats:sub>AR-knockout female mice. The PM<jats:sub>\u03a6<\/jats:sub> were treated with ISO, E<jats:sub>2<\/jats:sub>, and \u03b2<jats:sub>2<\/jats:sub>AR blocker ICI 118,551 for 24 h, and flow cytometric evaluations were done to assess their phenotypic expression. E<jats:sub>2<\/jats:sub> deficiency permitted the induction of CSC, which was characterized by cardiac dysfunctions, maladaptive myocardial hypertrophy, unresolved proinflammatory responses, and fibrosis. Nonetheless, E<jats:sub>2<\/jats:sub> presence\/supplementation during stress averted all the aforementioned adverse effects of chronic stress while preventing excessive depletion of \u03b2<jats:sub>2<\/jats:sub>AR. Also, we demonstrated that E<jats:sub>2<\/jats:sub> facilitates timely resolution of myocardial proinflammation to permit reparative functions by enhancing the polarization of CD86+ to CD206+ macrophages. However, this adaptive immunomodulation is hampered when \u03b2<jats:sub>2<\/jats:sub>AR is inhibited. Taken together, the outcomes of this study show that E<jats:sub>2<\/jats:sub> confers cardioprotection to prevent CSC <jats:italic>via<\/jats:italic> adaptive immunomodulation of macrophage phenotypes, and \u03b2<jats:sub>2<\/jats:sub>AR-mediated signaling is crucial for the polarizations of CD86+ to CD206+ macrophages.<\/jats:p>","DOI":"10.3389\/fcell.2021.737003","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T07:15:01Z","timestamp":1632813301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Estrogen Attenuates Chronic Stress-Induced Cardiomyopathy by Adaptively Regulating Macrophage Polarizations via \u03b22-Adrenergic Receptor Modulation"],"prefix":"10.3389","volume":"9","author":[{"given":"Hongjian","family":"Hou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Komla","family":"Adzika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqayya","family":"Rizvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8031","DOI":"10.1523\/JNEUROSCI.0653-18.2018","article-title":"Estrogen regulation of GRK2 inactivates kappa opioid receptor signaling mediating analgesia, but not aversion.","volume":"38","author":"Abraham","year":"2018","journal-title":"J. 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