{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:00:59Z","timestamp":1776852059530,"version":"3.51.2"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2022JQ\u2010886"],"award-info":[{"award-number":["2022JQ\u2010886"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypertensive heart disease is characterised by ventricular remodelling and interstitial fibrosis, in which dysregulation of the renin\u2013angiotensin system (RAS) plays a pivotal role. This study investigated whether the transcription factor CCAAT\/enhancer\u2010binding protein\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) attenuates hypertensive myocardial fibrosis and remodelling by modulating the angiotensin\u2010converting enzyme 2 (ACE2)\/angiotensin\u2010(1\u20137) [Ang\u2010(1\u20137)] axis. Eight\u2010week\u2010old male spontaneously hypertensive rats (SHR) received tail\u2010vein injection of lentiviral vectors encoding C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    short hairpin RNA (shRNA), or negative control (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096 per group), whereas Wistar\u2013Kyoto rats injected with saline served as normotensive controls. Twelve weeks after injection, blood pressure and echocardiographic parameters were assessed, and cardiac hypertrophy and fibrosis were evaluated by heart weight, heart weight\u2010to\u2010body weight ratio, histology, Masson's trichrome staining with quantitative morphometry, immunohistochemistry and Western blotting. Angiotensin II (Ang II) and Ang\u2010(1\u20137) levels were quantified in serum and myocardium, and circulating matrix metalloproteinase (MMP)\u20102\/9, interleukin\u20106 (IL\u20106) and monocyte chemotactic protein\u20101 (MCP\u20101) were measured by enzyme\u2010linked immunosorbent assay (ELISA). In parallel, primary rat cardiac fibroblasts were stimulated with Ang II and treated with lentiviral C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    overexpression in combination with ACE2\u2010specific or control small interfering RNA (siRNA) to examine ACE2\u2010dependent regulation of collagen I synthesis. C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    expression was markedly reduced in SHR myocardium compared with normotensive rats. C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    overexpression lowered arterial pressure, improved systolic and diastolic indices, and attenuated left ventricular hypertrophy and cardiomyocyte enlargement. Myocardial fibrosis was reduced, as shown by a smaller collagen\u2010positive area on Masson's trichrome staining and decreased collagen I, collagen III and transforming growth factor\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 (TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1) expression. C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    overexpression shifted the renin\u2013angiotensin system toward the ACE2\/Ang\u2010(1\u20137) axis, with higher ACE2 and Ang\u2010(1\u20137), lower angiotensin\u2010converting enzyme (ACE) and Ang II, and reduced IL\u20106 and MCP\u20101 levels, whereas MMP activity remained largely unchanged. In Ang II\u2013stimulated cardiac fibroblasts, C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    upregulated ACE2 and suppressed collagen I, while ACE2 knockdown abolished these antifibrotic effects, supporting an ACE2\u2010dependent mechanism. In contrast, C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    knockdown in\u00a0vivo had no significant impact on cardiac function, remodelling, fibrosis, inflammation, or RAS components. Myocardial C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    expression is reduced in hypertensive rats, and its restoration markedly limits hypertension\u2010induced cardiac injury. C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    overexpression lowers blood pressure, improves systolic and diastolic function and attenuates left ventricular hypertrophy, fibrosis and inflammation. These benefits are associated with a shift from the ACE\/Ang II towards the ACE2\/Ang\u2010(1\u20137) axis and reduced collagen accumulation, supporting C\/EBP\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010mediated ACE2 activation as a potential therapeutic strategy for hypertensive cardiac remodelling.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71139","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:56:06Z","timestamp":1775800566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting C\/\n                    <scp>\n                      <b>EBP<\/b>\n                    <\/scp>\n                    <i>\n                      <b>\n                        <i>\u03b2<\/i>\n                      <\/b>\n                    <\/i>\n                    to Suppress Myocardial Fibrosis in Hypertensive Heart Disease: Role of the\n                    <scp>\n                      <b>ACE2<\/b>\n                    <\/scp>\n                    \/Ang\u2010(1\u20137) Pathway"],"prefix":"10.1111","volume":"30","author":[{"given":"Yuanyuan","family":"Tie","sequence":"first","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bincheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donggang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-0912","authenticated-orcid":false,"given":"Ping","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiology Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 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