{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:14:04Z","timestamp":1790122444110,"version":"4.0.1"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:sec id=\"jah311122-sec-0001\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Atherosclerosis is a progressive arterial disease characterized by chronic inflammation and plaque formation in blood vessel walls. ELABELA, an endogenous ligand for the G protein\u2010coupled receptor APJ (apelin peptide jejunum, apelin receptor), has multiple pharmacological activities for protecting the cardiovascular system. This study aimed to determine the potential antiatherosclerotic effect of ELABELA and reveal the underlying mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311122-sec-0002\" xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We enrolled a cohort consisting of patients with and without atherosclerosis to determine the relationship between plasma ELABELA levels and atherosclerosis severity. The potential therapeutic action of ELA\u201021 (ELABELA\u201021) on atherosclerosis in high\u2010fat diet\u2010fed\n              <jats:italic toggle=\"no\">ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice was evaluated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311122-sec-0003\" xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Plasma ELABELA levels were significantly reduced and negatively correlated with plasma MMP2 (matrix metallopeptidase 2) and MMP9 (matrix metallopeptidase 9) levels in patients with atherosclerosis and high\u2010fat diet\u2010induced atherosclerotic\n              <jats:italic toggle=\"no\">ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Plasma ELABELA levels exhibited a potential diagnostic value for patients with atherosclerosis. Applying ELA\u201021 significantly decreased the atherosclerotic plaque area and inflammation in the aortas of the\n              <jats:italic toggle=\"no\">ApoE<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. ELA\u201021 administration modulated the balance between M1 and M2 macrophages in the abdominal cavity and aorta roots toward a more anti\u2010inflammatory status, accompanied by reduced MMP2, MMP9, and PRR ([pro]renin receptor), and enhanced macrophage APJ, ACE (angiotensin\u2010converting enzyme), and ACE2 (angiotensin\u2010converting enzyme 2) protein expression in plaques within aortic roots and decreased plasma soluble PRR levels. In\u00a0vitro, ELA\u201021 effectively suppressed oxidized low\u2010density lipoprotein\u2010induced foam cell formation and lipopolysaccharide\/interferon\u2010\u03b3\u2010induced M1 polarization in cultured macrophages. Interestingly, the anti\u2010inflammatory effect of ELA\u201021 was further enhanced by APJ inhibitor ML221 [4\u2010oxo\u20106\u2010((pyrimidin\u20102\u2010ylthio)methyl)\u20104H\u2010pyran\u20103\u2010yl 4\u2010nitrobenzoate], accompanied by elevated\n              <jats:italic toggle=\"no\">ACE<\/jats:italic>\n              and\n              <jats:italic toggle=\"no\">ATP6AP2<\/jats:italic>\n              (ATPase, H\n              <jats:sup>+<\/jats:sup>\n              \u2010transporting, lysosomal accessory protein 2) and reduced\n              <jats:italic toggle=\"no\">ACE2<\/jats:italic>\n              mRNA levels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311122-sec-0004\" xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data highlighted the diagnostic and therapeutic potential of ELABELA on atherosclerosis. ELA\u201021 protects against atherosclerosis by inhibiting atherosclerotic plaque formation and promoting a more stable plaque phenotype, possibly via restoring the M1\/M2 macrophage balance, enhancing macrophage ACE and ACE2 expression, and inhibiting the PRR system. ELABELA may be a novel diagnostic biomarker and candidate therapeutic target for atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.041261","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T10:25:41Z","timestamp":1752488741000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["ELABELA Ameliorates Atherosclerosis Through Restoring the M1\/M2 Macrophage Balance in\n            <i>ApoE<\/i>\n            <sup>\u2212\/\u2212<\/sup>\n            Mice"],"prefix":"10.1161","volume":"14","author":[{"given":"Le","family":"Tang","sequence":"first","affiliation":[{"name":"Jiangxi University of Chinese Medicine","place":["Nanchang, China"]},{"name":"Temple University","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yi","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese 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