{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:01:09Z","timestamp":1790798469467,"version":"4.1.0"},"reference-count":91,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The role of leukocytes in the pathogenesis of right ventricular (RV) dysfunction (RVD) associated with heart failure with preserved ejection fraction (HFpEF) remains poorly defined, partially due to the lack of suitable small animal models. Here, we followed a translational research approach by establishing a murine HFpEF model developing manifest RVD and analyzed human HFpEF cohorts to study the mechanistic link between leukocytes and RVD in HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Young (&lt;20-week-old) and aged (&gt;80-week-old) male and female C57BL\/6J mice were divided into 4 experimental groups: chow, HFpEF (L-NAME [N\u03c9-nitro-L-arginine methyl ester] plus a high-fat diet), chronic hypoxia (10% O\n                      <jats:sub>2<\/jats:sub>\n                      ), and HFpEF plus hypoxia (RV-HFpEF). Biventricular function and myeloid cell dynamics were assessed across groups. To test whether myeloid cells are causally involved in the development of RV remodeling in HFpEF, we treated RV-HFpEF mice with a colony-stimulating factor 1 receptor inhibitor to deplete myeloid cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      RV-HFpEF resulted in left ventricular diastolic dysfunction, indicated by increased E\/E\u2032 ratio, reduced global longitudinal peak strain, smaller end-diastolic diameters, and increased isovolumetric relaxation time compared with chow. RV-HFpEF animals developed RV hypertrophy and RVD, evident as increased Fulton index as well as elevated RV systolic pressure and reduced tricuspid annular plane systolic excursion, respectively. Total leukocyte, monocyte, and macrophage counts were elevated in RV tissue from RV-HFpEF mice compared with RV tissue from chow mice and left ventricular tissue from young and aged RV-HFpEF animals. These findings were confirmed by unbiased proteomic analyses of RV tissue from RV-HFpEF mice, demonstrating an increased abundance of proteins involved in activation of the innate immune system, macrophage chemotaxis, and leukocyte migration when compared with left ventricular tissue and the other experimental groups. Fate-mapping experiments revealed that recruited monocyte-derived macrophages became the main source of total cardiac macrophages in RV tissue from RV-HFpEF mice. Depletion of myeloid cells was associated with lower RVSP profiles in RV-HFpEF mice compared with controls. In RV biopsies from patients with HFpEF, we found increased expression of adhesion molecules, fibrotic markers, and inflammatory transcripts, as well as an association between RVD and CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We demonstrate that dysregulated myeloid cell dynamics are associated with, and directly contribute to, the pathogenesis of RVD associated with HFpEF in humans and mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.078476","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:00:21Z","timestamp":1787043621000},"page":"1200-1220","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Myeloid Cell Expansion Propels Right Ventricular Dysfunction in HFpEF Through Sterile Inflammation"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1847-5378","authenticated-orcid":true,"given":"Lara","family":"Jaeschke","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-2447","authenticated-orcid":true,"given":"Ceren","family":"Koc\u0327ana","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Maria","family":"Chitroceanu","sequence":"additional","affiliation":[{"name":"Campus Virchow Klinikum (A.M.C., D.Z., K.F., E.R., S.v.L., C.O., F.E.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9434-3862","authenticated-orcid":true,"given":"Annika","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9991-6044","authenticated-orcid":true,"given":"Hannah","family":"Kleitke","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-0643","authenticated-orcid":true,"given":"Pauline","family":"Fahjen","sequence":"additional","affiliation":[{"name":"Proteomics Platform, Max-Delbr\u00fcck-Center for Molecular Medicine, Berlin, Germany (P.F., P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4088-3796","authenticated-orcid":true,"given":"Justus","family":"Kamp","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."},{"name":"Junior Research Group, Cardiac Aging and Nutrition, German Institute of Human Nutrition Potsdam\u2013Rehbruecke, Nuthetal, Germany (J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-9595","authenticated-orcid":true,"given":"David","family":"Faidel","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-7724","authenticated-orcid":true,"given":"Erik","family":"Asmus","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. G.G.S., S.v.L., N.B., C.O., N.H., P.M., F.E., W.M.K., J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meiser","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., L.A.v.d.O., K.B., J.L.G., N.B., N.H., J.G.), Deutsches Herzzentrum der Charit\u00e9 (DHZC), Berlin, Germany."},{"name":"Institute of Physiology (L.J., C.K., A.W., H.K., J.K., D.F., E.A., M.M., P.-L.P., L.A.v.d.O., S.S., J.L.G., N.H., W.M.K., J.G.), Germany."},{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2785-9005","authenticated-orcid":true,"given":"Efstathios G.","family":"Stamatiades","sequence":"additional","affiliation":[{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Berlin, Germany (E.G.S., K.W.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-4496","authenticated-orcid":true,"given":"Karolin W.","family":"Hublitz","sequence":"additional","affiliation":[{"name":"Campus Virchow Klinikum, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin (L.J., C.K., A.M.C., A.W., H.K., J.K., D.F., E.A., M.M., E.G.S., K.W.H., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F., E.R., N.B., N.H., P.M., F.E., J.G.), Germany."},{"name":"Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Berlin, Germany (E.G.S., K.W.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Zach","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany (L.J., C.K., A.M.C., H.K., J.K., D.F., E.A., V.Z., D.Z., P.-L.P., L.A.v.d.O., K.B., S.S., J.L.G., K.F. 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