{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T21:59:11Z","timestamp":1794434351914,"version":"4.9.1"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Women with heart failure with reduced ejection fraction (HFrEF) experience greater symptom burden than men, potentially due to skeletal muscle dysfunction. Skeletal muscle abnormalities are linked to systemic low-grade inflammation, a hallmark of HFrEF pathophysiology, and may be driven by altered inflammatory regulation of skeletal muscle homeostasis. In patients with HFrEF and age-matched controls, we investigated sex differences in skeletal muscle inflammation, muscle stem cells, fibro-adipogenic progenitor cells, and their associations with skeletal muscle mass and strength.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Participants underwent dual x-ray absorptiometry, cardiopulmonary exercise testing, and dynamometry. Vastus lateralis muscle biopsies were analyzed by flow cytometry to quantify immune cell populations, muscle stem cells, and fibro-adipogenic progenitor cells. Outcomes were log-transformed and analyzed using linear regression with sex-by-HFrEF interaction. Between-group differences were expressed as geometric mean ratios (GMRs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We included 86 patients with HFrEF and 41 age- and sex-matched healthy controls (mean age, 71\u00b17 years; 32% women). Skeletal muscle immune cell composition differed by sex in HFrEF, with significant sex-by-HFrEF interactions for macrophage fraction (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006), lymphocyte content (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.045), and lymphocyte fraction (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.039). In HFrEF, women showed an increased lymphocyte fraction (GMR, 1.27 [1.06\u20131.53];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.014), whereas men had an increased macrophage content (GMR, 1.75 [1.16\u20132.64];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.009). Macrophage content was associated with greater muscle mass and strength in women (mass, R=0.42,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.014; strength, R=0.42,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.013), but with reduced mass and strength in men (mass, R=\u22120.25,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.017; strength, R=\u22120.21,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.046). Muscle stem cells (GMR, 1.92 [0.99\u20133.74];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.054) and fibro-adipogenic progenitor cells (GMR, 1.72 [1.03\u20132.85];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.038) were reduced in HFrEF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Skeletal muscle immune cell alterations, particularly macrophage and lymphocyte imbalances, are associated with muscle dysfunction in HFrEF, exhibiting distinct sex-specific patterns. These findings demonstrate sex-specific skeletal muscle inflammation and dysfunction in HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.014062","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:00:17Z","timestamp":1787821217000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Sex Differences in Skeletal Muscle Inflammation and Dysfunction in Patients With Heart Failure and Reduced Ejection Fraction"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2871-0584","authenticated-orcid":true,"given":"Andreas Bugge","family":"Tinggaard","sequence":"first","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, Denmark (A.B.T., H.W.)."},{"name":"Department of Clinical Medicine (A.B.T., M.B., H.N., H.W.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-7132","authenticated-orcid":true,"given":"Jakob","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedicine (J.W., J.F., E.B., N.J.), Aarhus University, Denmark."},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark (J.W., J.F., M.B., J.B., N.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-6512","authenticated-orcid":true,"given":"Jean","family":"Farup","sequence":"additional","affiliation":[{"name":"Department of Biomedicine (J.W., J.F., E.B., N.J.), Aarhus University, Denmark."},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark (J.W., J.F., M.B., J.B., N.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Bjerre","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine (A.B.T., M.B., H.N., H.W.), Aarhus University, Denmark."},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark (J.W., J.F., M.B., J.B., N.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Brorson","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark (J.W., J.F., M.B., J.B., N.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Chousterman","sequence":"additional","affiliation":[{"name":"Inserm U942 Mascot, Universit\u00e9 de Paris, France (B.C.)."},{"name":"Department of Anesthesia and Critical Care, Lariboisi\u00e8re University Hospital, Paris, France (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"B\u00f6rgeson","sequence":"additional","affiliation":[{"name":"Department of Biomedicine (J.W., J.F., E.B., N.J.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-7141","authenticated-orcid":true,"given":"P. Christian","family":"Schulze","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine I, University Hospital Jena, Germany (P.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"N\u00f8rrelund","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine (A.B.T., M.B., H.N., H.W.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5613-7274","authenticated-orcid":true,"given":"Niels","family":"Jessen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine (J.W., J.F., E.B., N.J.), Aarhus University, Denmark."},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark (J.W., J.F., M.B., J.B., N.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9753-4142","authenticated-orcid":true,"given":"Henrik","family":"Wiggers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, Denmark (A.B.T., H.W.)."},{"name":"Department of Clinical Medicine (A.B.T., M.B., H.N., H.W.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz835"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.081"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2006.10.012"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.0924"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs381"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2015.01.008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07015-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12603"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.033571"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.1.280"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(02)01740-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12488"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.011471"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1453"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-019-0189-y"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.14.1690"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3062"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-780882"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061386"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1274816"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.054"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00735.2009"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03093-6"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.210110"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.074"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3710"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_3_3_29_2","first-page":"919","article-title":"The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.","volume":"132","author":"Guyatt GH","year":"1985","unstructured":"Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, Berman LB. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J. 1985;132:919\u2013923","journal-title":"Can Med Assoc J"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00127.2021"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.102008"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaa117"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.02.055"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.11.050"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054651"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-019-0257-3"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-024-09668-6"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-017-0354-4"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-37229-3"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00333.2021"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-019-0205-2"},{"key":"e_1_3_3_42_2","first-page":"934","article-title":"1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokines in human macrophages.","volume":"30","author":"Villaggio B","year":"2012","unstructured":"Villaggio B, Soldano S, Cutolo M. 1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokines in human macrophages. Clin Exp Rheumatol. 2012;30:934\u2013938","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101320-125133"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-63185-3"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu16152464"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046038"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00778-x"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14396-9"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03197-9"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1577"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-15-35"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14417"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101098"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3869"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.001"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139617"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.01.014"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.25.3060"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308030"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9593-0"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800973R"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12828"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900519R"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111974"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.04.006"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahjo.2022.100093"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.125.014062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:00:22Z","timestamp":1787821222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.125.014062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":65,"alternative-id":["10.1161\/CIRCHEARTFAILURE.125.014062"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.125.014062","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"assertion":[{"value":"2025-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e014062"}}