{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:33:00Z","timestamp":1793046780667,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2023,11,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Eight-week-old male and female C57BL\/6J mice received either N\n                      <jats:sup>\u03b3<\/jats:sup>\n                      -nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db\/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1\u03b2 (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti\u2013IL-1\u03b2 antibody were utilized to deplete macrophages and IL-1\u03b2, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      N\n                      <jats:sup>\u03b3<\/jats:sup>\n                      -nitro-L-arginine methyl ester\/high-fat diet\u2013treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1\u03b2 in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in N\n                      <jats:sup>\u03b3<\/jats:sup>\n                      -nitro-L-arginine methyl ester\/high-fat diet\u2013treated mice, and IL-1\u03b2 depletion also attenuated PH in N\n                      <jats:sup>\u03b3<\/jats:sup>\n                      -nitro-L-arginine methyl ester\/high-fat diet\u2013treated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell\u2013derived IL-1\u03b2 as an important contributor to PH in HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.123.323119","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T05:01:03Z","timestamp":1699246863000},"page":"885-898","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Myeloid Cell Derived IL1\u03b2 Contributes to Pulmonary Hypertension in HFpEF"],"prefix":"10.1161","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8457-6722","authenticated-orcid":true,"given":"Vineet","family":"Agrawal","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."},{"name":"Tennessee Valley Healthcare System Nashville Veteran Affairs Hospital (V.A., D.F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8923-1344","authenticated-orcid":true,"given":"Jonathan A.","family":"Kropski","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care (J.A.K., J.J.G., C.S.M., T.B., M.H.T., S.G., E.J.C., J.D.W., A.R.H., N.L.F.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8244-7831","authenticated-orcid":true,"given":"Jason J.","family":"Gokey","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care (J.A.K., J.J.G., C.S.M., T.B., M.H.T., S.G., E.J.C., J.D.W., A.R.H., N.L.F.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kobeck","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology (M.B.M., K.T.M., K.T.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1342-4457","authenticated-orcid":true,"given":"Katherine T.","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."},{"name":"Division of Clinical Pharmacology (M.B.M., K.T.M., K.T.M.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki L.","family":"Fortune","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care (J.A.K., J.J.G., C.S.M., T.B., M.H.T., S.G., E.J.C., J.D.W., A.R.H., N.L.F.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy S.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Meoli","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."},{"name":"Tennessee Valley Healthcare System Nashville Veteran Affairs Hospital (V.A., D.F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-4647","authenticated-orcid":true,"given":"Ken","family":"Monahan","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ru Su","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Blackwell","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha H.","family":"Talati","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gladson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-3088","authenticated-orcid":true,"given":"Erica J.","family":"Carrier","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"West","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2755-5845","authenticated-orcid":true,"given":"Anna R.","family":"Hemnes","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (V.A., E.K., K.T.M., D.F.M., K.M., Y.R.S., D.K.G.), Department of Medicine, Vanderbilt University Medical Center, Nashville, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247987"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.031608"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319971"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001079"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1100-z"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/2045894019895452"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3791\/50912"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/1354750X.2019.1710256"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/2045893217745019"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/791699"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1972"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.199512"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.17.533161"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.18.491687"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-3-37"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.06.008"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.08.074"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.11.051"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-004843"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041886"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314555"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018935"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.076075"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14332"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1956"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006414"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3172"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202110-2274OC"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.08.003"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-61"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.123.323119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:47:35Z","timestamp":1715561255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.123.323119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,10]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11,10]]}},"alternative-id":["10.1161\/CIRCRESAHA.123.323119"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.123.323119","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,10]]},"assertion":[{"value":"2023-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}