{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:04:08Z","timestamp":1789448648072,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 ES007141"],"award-info":[{"award-number":["T32 ES007141"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31 HL165820"],"award-info":[{"award-number":["F31 HL165820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 HL157800"],"award-info":[{"award-number":["R21 HL157800"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL136496"],"award-info":[{"award-number":["R01 HL136496"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ischemic heart disease is a primary cause of death for men and women in the United States. Recent epidemiologic findings, however, suggest that premenopausal women have inherent protection from many cardiovascular pathologies compared to age\u2010matched men, which is lost with menopause. We and others have documented similar protective signaling in animal models, with females exhibiting protection from ischemic injury that is lost with ovariectomy (OVX). Furthermore, in recent studies, we demonstrated that the loss of alcohol dehydrogenase 5 (ADH5) blocked sex\u2010specific cardioprotection in females, but activation of aldehyde dehydrogenase 2 (ALDH2) provided a rescue. ADH5 and ALDH2 both metabolize formaldehyde to formate, potentially implicating formate in female\u2010specific cardioprotection. Therefore, the objective of this study was to examine a role for formate during ischemic injury in female hearts using wild\u2010type (WT) and ADH5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. We also aimed to explore estrogen\u2010dependent effects by using ovariectomized (OVX) WT mice. To assess the protective effects of formate in intact WT and ADH5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    female mice, as well as OVX WT female mice, hearts were Langendorff\u2010perfused and subjected to ischemia\/reperfusion (I\/R) injury. Since formate is used in one\u2010carbon metabolism (OCM), select OCM enzymes were also probed via western blot. Importantly, we found that formate significantly reduced infarct size in intact ADH5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    female hearts subjected to I\/R injury, but formate was without effect in intact WT female hearts. Additionally, formate failed to reduce I\/R injury in OVX WT female hearts, despite OVX WT female hearts exhibiting reduced ADH5 and ALDH2 activity. However, we noted that the expression of certain OCM enzymes was downregulated in OVX WT female hearts versus intact WT females, which may prevent proper formate utilization by OCM in OVX WT female hearts. Furthermore, blockage of formate import into OCM in intact WT female hearts also exacerbated I\/R injury. Taken together, our findings support formate utilization by OCM as a key component of cardioprotective signaling in female hearts, with estrogen acting as a potential mediator.\n                  <\/jats:p>","DOI":"10.1096\/fba.2025-00237","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:11:11Z","timestamp":1765609871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Formate Reduces Ischemic Injury in Female Hearts Lacking Alcohol Dehydrogenase 5"],"prefix":"10.1096","volume":"7","author":[{"given":"Haley","family":"Garbus\u2010Grant","sequence":"first","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obialunanma V.","family":"Ebenebe\u2010Kasonde","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raihan","family":"Kabir","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-5962","authenticated-orcid":false,"given":"Mark J.","family":"Kohr","sequence":"additional","affiliation":[{"name":"Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12270"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02710-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00005-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.968792"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.1.252"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12471-010-0841-y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1107"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00681.2015"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177315"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313956"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000202707.79018.0a"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.868729"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.213645"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01291.2005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.12.1215"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00528-4"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.5812\/ijem-135101"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008243430801"},{"key":"e_1_2_11_20_1","article-title":"Hormone Therapy for Preventing Cardiovascular Disease in Post\u2010Menopausal Women","volume":"3","author":"Boardman H. 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