{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:56:36Z","timestamp":1790290596121,"version":"4.1.0"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac failure is the primary cause of death in most patients with pulmonary arterial hypertension (PH). As pleiotropic cytokines, human resistin (Hresistin) and its rodent homolog, resistin\u2010like molecule \u03b1, are mechanistically critical to pulmonary vascular remodeling in PH. However, it is still unclear whether activation of these resistin\u2010like molecules can directly cause PH\u2010associated cardiac dysfunction and remodeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In this study, we detected Hresistin protein in right ventricular (RV) tissue of patients with PH and elevated resistin\u2010like molecule expression in RV tissues of rodents with RV hypertrophy and failure. In a humanized mouse model, cardiac\u2010specific Hresistin overexpression was sufficient to cause cardiac dysfunction and remodeling. Dilated hearts exhibited reduced force development and decreased intracellular Ca\n              <jats:sup>2+<\/jats:sup>\n              transients. In the RV tissues overexpressing Hresistin, the impaired contractility was associated with the suppression of protein kinase A and AMP\u2010activated protein kinase. Mechanistically, Hresistin activation triggered the inflammation mediated by signaling of the key damage\u2010associated molecular pattern molecule high\u2010mobility group box 1, and subsequently induced pro\u2010proliferative Ki67 in RV tissues of the transgenic mice. Intriguingly, an anti\u2010Hresistin human antibody that we generated protected the myocardium from hypertrophy and failure in the rodent PH models.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data indicate that Hresistin is expressed in heart tissues and plays a role in the development of RV dysfunction and maladaptive remodeling through its immunoregulatory activities. Targeting this signaling to modulate cardiac inflammation may offer a promising strategy to treat PH\u2010associated RV hypertrophy and failure in humans.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027621","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T02:03:27Z","timestamp":1679018607000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-800X","authenticated-orcid":false,"given":"Qing","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-9399","authenticated-orcid":false,"given":"Udeshika","family":"Kariyawasam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4081-4207","authenticated-orcid":false,"given":"Xiaomei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Anesthesiology Qilu Hospital, Cheeloo College of Medicine, Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"},{"name":"Department of Cardiovascular Medicine Xiangya Hospital, Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0752-5438","authenticated-orcid":false,"given":"John T.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2363-3762","authenticated-orcid":false,"given":"Wei Dong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9232-2434","authenticated-orcid":false,"given":"Roger A.","family":"Johns","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00040.2020"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-021-10123-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90526.2008"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6527com"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00168.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.04.006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.15.4046"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000073999.07698.33"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011251"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200912-1827ED"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306710"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904021"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00279.2013"},{"issue":"110","key":"e_1_3_2_16_2","article-title":"S100a11 mediates hypoxia\u2010induced mitogenic factor (HIMF)\u2010induced smooth muscle cell migration, vesicular exocytosis, and nuclear activation","volume":"10","author":"Fan C","year":"2011","unstructured":"Fan C, Fu Z, Su Q, Angelini DJ, Van Eyk J, Johns RA. 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