{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:48:06Z","timestamp":1791776886906,"version":"4.3.4"},"reference-count":31,"publisher":"Portland Press Ltd.","issue":"24","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["APP1102882"],"award-info":[{"award-number":["APP1102882"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:p>Mineralocorticoid receptor antagonists (MRAs) reduce hypertension, inflammation and tissue injury in human and experimental diabetes. Inflammation and injury in diabetic hearts and kidneys is also dependent on infiltrating macrophages. Therefore, we hypothesised that the tissue protective effects of MRAs in diabetes are dependent on mineralocorticoid receptor (MR) signalling in macrophages. To evaluate this hypothesis, transgenic mice with intact myeloid MR (MRflox\/flox) or myeloid MR deficiency (MRflox\/flox LysMCre) were developed on the hypertensive endothelial nitric oxide synthase deficient (Nos3-\/-) mouse strain. Groups of these mice were made diabetic with streptozotocin and were assessed after 15 weeks for development of hypertension, cardiomyopathy and nephropathy. Nos3-\/- mice with myeloid MR deficiency had equivalent diabetes and hypertension as myeloid MR intact controls but were protected against cardiac and renal function impairment. In diabetic hearts, myeloid MR deficiency reduced cardiomyocyte hypertrophy, capillary loss and fibrosis in association with reduced macrophage accumulation and a switch from an M1 to an M2 macrophage phenotype. In diabetic kidneys, myeloid MR deficiency reduced renal dysfunction (elevated plasma cystatin C) but did not protect against albuminuria, glomerulosclerosis or tubular damage; this was associated with a partial reduction in glomerular macrophages and an M1 to M2 macrophage phenotype switch. Therefore, MR signalling in macrophages promotes dysfunction in the diabetic heart and kidneys of Nos3-\/- mice without affecting hypertension. Furthermore, abolishing macrophage MR signalling provides greater protection to hearts than kidneys during type 1 diabetes and hypertension, giving new insight into the mechanisms by which MRAs suppress tissue injury during diabetes.<\/jats:p>","DOI":"10.1042\/cs20256132","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T07:51:11Z","timestamp":1764748271000},"page":"1675-1689","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deficiency of mineralocorticoid receptor signalling in myeloid cells protects cardiac and kidney function in hypertensive diabetic mice"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-3092","authenticated-orcid":false,"given":"Gregory H.","family":"Tesch","sequence":"first","affiliation":[{"name":"1Monash Health (Department of Nephrology), Clayton, Victoria, Australia"},{"name":"2Monash University School of Clinical Sciences at Monash Health, Clayton, Victoria, Australia"},{"name":"3Monash University Centre for Inflammatory Diseases, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyce","family":"Ozols","sequence":"additional","affiliation":[{"name":"1Monash Health (Department of Nephrology), Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Morgan","sequence":"additional","affiliation":[{"name":"4Hudson Institute of Medical Research, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morag J.","family":"Young","sequence":"additional","affiliation":[{"name":"4Hudson Institute of Medical Research, Clayton, Victoria, Australia"},{"name":"5Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"},{"name":"6Baker Department of Cardiometabolic Health and Disease, University of Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Nikolic-Paterson","sequence":"additional","affiliation":[{"name":"1Monash Health (Department of Nephrology), Clayton, Victoria, Australia"},{"name":"2Monash University School of Clinical Sciences at Monash Health, Clayton, Victoria, Australia"},{"name":"3Monash University Centre for Inflammatory Diseases, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"2025122309064331600_CS-2025-6132C1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10741-020-09987-z","article-title":"Pathogenesis of chronic heart failure: cardiovascular aging, risk factors, comorbidities, and disease modifiers","volume":"27","author":"Triposkiadis","year":"2022","journal-title":"Heart Fail. 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