{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:24:36Z","timestamp":1788805476708,"version":"build-2803163510"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,8,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical picture that is closely related to extracardiac comorbidities such as obesity, hypertension, and diabetes and is associated with chronic, low-grade systemic inflammation. Previous studies on myocardial biopsies of patients with HFpEF showed intramyocardial inflammatory activity, suggesting that the inflammatory processes in HFpEF are predominantly systemic and exhibit compartment-specific patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We performed single-cell RNA sequencing of peripheral blood mononuclear cells of patients with HFpEF (n=6), patients with heart failure with reduced ejection fraction (HFrEF, n=8), and healthy controls (n=7), taking obesity status into account. For validation, bulk RNA sequencing was performed on whole blood samples. In parallel, the systemic immune cell response was investigated in an HFpEF mouse model (induced by a high-fat diet plus\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <jats:sub>\u03c9<\/jats:sub>\n                      -nitro-L-arginine methyl ester hydrochloride [L-NAME]), with one group additionally administered the anti-inflammatory agent nitro-oleic acid (NO\n                      <jats:sub>2<\/jats:sub>\n                      -OA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Analysis of human peripheral blood mononuclear cells revealed an HFpEF-specific inflammatory fingerprint, which manifested in obesity-related increased expression of cytokine signaling genes (eg,\n                      <jats:italic toggle=\"yes\">CCL2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TNF<\/jats:italic>\n                      ) and obesity-independent increases in mitochondrial-associated activity. In the mouse model, HFpEF animals showed a comparable increase in inflammatory markers, with treatment with nitro-oleic acid leading to a partial normalization of immunologic signatures and a significant improvement in diastolic function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our results demonstrate that the immune cells of patients with HFpEF are characterized by a distinct transcriptional immune signature that differs from that of patients with HFrEF analyzed in this study. The conserved immunologic signatures between the human and murine data sets analyzed here, and the beneficial effect of nitro-oleic acid in the preclinical model induced by high-fat diet and L-NAME, provide translational insights and generate hypotheses for personalized interventions in HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.326249","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:00:10Z","timestamp":1753434010000},"page":"682-698","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Circulating Immune Cell Signature Analysis in HFpEF Across Species"],"prefix":"10.1161","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0273-3614","authenticated-orcid":true,"given":"Jasmin Marga","family":"Kneuer","sequence":"first","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8519-0661","authenticated-orcid":true,"given":"Marion","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Clinic for General and Interventional Cardiology\/Angiology (M.M., A.K.)"},{"name":"Agnes Wittenborg Institute for Translational Cardiovascular Research (AWIHK), Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW), Ruhr-Universit\u00e4t Bochum, Bad Oeynhausen, Germany (M.M., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-8981","authenticated-orcid":true,"given":"Stephan","family":"Erbe","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-4289","authenticated-orcid":true,"given":"Karoline Elizabeth","family":"Kokot","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4380-4821","authenticated-orcid":true,"given":"Sebastian","family":"Rosch","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center at University of Leipzig, Leipzig, Germany (S.R., P.L.)."},{"name":"Department of Cardiology, Universit\u00e4tsmedizin Johannes Gutenberg-University, Mainz, Germany (S.R., P.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"M\u00fcller-Kozarez","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie Charlotte","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-1154","authenticated-orcid":true,"given":"Christina","family":"Maeder","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Kardiologie, Universit\u00e4tsklinikum Leipzig, Leipzig, Germany (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., J.-N.B.)."},{"name":"Central German Heart Alliance (J.M.K., S.E., K.E.K., I.M.-K., S.C.S., C.M., S.F.H., S.G., R.W., U.L., 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