{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T22:58:46Z","timestamp":1784329126617,"version":"3.55.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,11,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Pathological cardiac hypertrophy stands as a pivotal mechanism contributing to diverse cardiovascular diseases, ultimately leading to heart failure. Despite its clinical significance, the intricate molecular mechanisms instigating pathological cardiac hypertrophy remain inadequately understood. In this study, we aim to further reveal its complex pathogenesis by exploring the role of Fas apoptotic inhibitory molecule 2 (FAIM2) in modulating pathological cardiac hypertrophy.<\/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              We used phenylephrine\u2010induced hypertrophic cardiomyocytes and also generated cardiac\u2010specific knockout mice and adeno\u2010associated virus serotype 9\u2010Faim2 mice to evaluate the function of FAIM2 in pathological myocardial hypertrophy. Furthermore, unbiased RNA\u2010sequencing analysis was used to identify the direct target and corresponding molecular events contributing to FAIM2 function. Ultimately, our study revealed a downregulation of FAIM2 expression in phenylephrine\u2010induced hypertrophic cardiomyocytes and pressure overload\u2013induced hypertrophic hearts. FAIM2 exhibited a significant attenuation of phenylephrine\u2010induced enlargement of primary neonatal rat cardiomyocytes, whereas FAIM2 knockdown aggravated the hypertrophic response. Furthermore,\n              <jats:italic>Faim2<\/jats:italic>\n              gene knockout significantly exacerbated cardiac hypertrophy and heart fibrosis in\u00a0vivo. Mechanistic investigations unveiled that FAIM2 exerts its inhibitory effect by suppressing TAK1\u2010JNK1\/2\u2010p38 MAPK signaling cascades, thereby mitigating cardiac hypertrophy.\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 findings position FAIM2 as a novel negative regulator of pathological cardiac hypertrophy through its inhibitory action on mitogen\u2010activated protein kinase signaling activation. This identification of FAIM2's role provides crucial insights that may pave the way for the development of effective therapeutic strategies aimed at mitigating pathological cardiac hypertrophy, addressing a critical need in cardiovascular disease management.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.034257","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T04:08:17Z","timestamp":1731730097000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Fas Apoptosis Inhibitory Molecule 2 Inhibits Pathological Cardiac Hypertrophy by Regulating the MAPK Signaling Pathway"],"prefix":"10.1161","volume":"13","author":[{"given":"Huaping","family":"Zhong","sequence":"first","affiliation":[{"name":"Suzhou Medical College of Soochow University Suzhou China"},{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Gannan Innovation and Translational Medicine Research Institute Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Xie","sequence":"additional","affiliation":[{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[{"name":"Wuhan Britain\u2010China School Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhisheng","family":"Duan","sequence":"additional","affiliation":[{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyou","family":"Liu","sequence":"additional","affiliation":[{"name":"Heart Center The First Affiliated Hospital of Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0889-1887","authenticated-orcid":false,"given":"Wei","family":"Liao","sequence":"additional","affiliation":[{"name":"Gannan Medical University Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-684X","authenticated-orcid":false,"given":"Yijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Suzhou Medical College of Soochow University Suzhou China"},{"name":"Department of Hematology The First Affiliated Hospital of Gannan Medical University Ganzhou China"},{"name":"The Endemic Disease (Thalassemia) Clinical Research Center of Jiangxi Province Ganzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12555"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08192"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150804110412"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx130"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.06.004"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.04898"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321849"},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","unstructured":"Yang X Chang HC Tatekoshi Y Mahmoodzadeh A Balibegloo M Najafi Z Wu R Chen C Sato T Shapiro J et\u00a0al. 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