{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:05:43Z","timestamp":1791223543801,"version":"4.1.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP2HL137166 and 1R01HL161212 to M.S.M., 1K08HL1533956 to V.A., T32GM007347 and F30HL151069 to C.D.S."],"award-info":[{"award-number":["DP2HL137166 and 1R01HL161212 to M.S.M., 1K08HL1533956 to V.A., T32GM007347 and F30HL151069 to C.D.S."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["IPLOI34760558 and 19EIA34480023 to M.S.M., 20PRE35080177to C.D.S."],"award-info":[{"award-number":["IPLOI34760558 and 19EIA34480023 to M.S.M., 20PRE35080177to C.D.S."]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvad093","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T08:28:50Z","timestamp":1686731330000},"page":"2312-2328","source":"Crossref","is-referenced-by-count":52,"title":["Immune profiling of murine cardiac leukocytes identifies triggering receptor expressed on myeloid cells 2 as a novel mediator of hypertensive heart failure"],"prefix":"10.1093","volume":"119","author":[{"given":"Charles Duncan","family":"Smart","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University , 2201 West End Ave, Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Fehrenbach","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center (VUMC) , 2215 Garland Avenue, P415D MRB IV, Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean W","family":"Wassenaar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center (VUMC) , 1311 Medical Center Dr, Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center (VUMC) , 1311 Medical Center Dr, Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki L","family":"Fortune","sequence":"additional","affiliation":[{"name":"VA Tennessee Valley Healthcare System , Nashville, TN 37212 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra D","family":"Dixon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center (VUMC) , 1311 Medical Center Dr, Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Cottam","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University , 2201 West End Ave, Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa H","family":"Hasty","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University , 2201 West End Ave, Nashville, TN 37235 ,","place":["USA"]},{"name":"VA Tennessee Valley Healthcare System , Nashville, TN 37212 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna R","family":"Hemnes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Pulmonary and Critical Care, Vanderbilt University Medical Center (VUMC) , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda C","family":"Doran","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center (VUMC) , 1311 Medical Center Dr, Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation , Vanderbilt University Medical Center (VUMC), Medical Center North A-5121, 1161 21st Ave South, Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2191-3485","authenticated-orcid":false,"given":"Deepak K","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center (VUMC) , 1311 Medical Center Dr, Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0407-634X","authenticated-orcid":false,"given":"Meena S","family":"Madhur","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University , 2201 West End Ave, Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center (VUMC) , 2215 Garland Avenue, P415D MRB IV, Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Medicine, Division of Cardiovascular Medicine, 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