{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:21:52Z","timestamp":1792794112748,"version":"4.5.0"},"reference-count":98,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2016,6,7]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>We have previously shown that systemic infusion of insulin-like growth factor-1 (IGF-1) exerts anti-inflammatory and antioxidant effects and reduces atherosclerotic burden in apolipoprotein E (Apoe)\u2013deficient mice. Monocytes\/macrophages express high levels of IGF-1 receptor (IGF1R) and play a pivotal role in atherogenesis, but the potential effects of IGF-1 on their function are unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              To determine mechanisms whereby IGF-1 reduces atherosclerosis and to explore the potential involvement of monocytes\/macrophages, we created monocyte\/macrophage\u2013specific IGF1R knockout (M\u03a6-IGF1R-KO) mice on an Apoe\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              background. We assessed atherosclerotic burden, plaque features of stability, and monocyte recruitment to atherosclerotic lesions. Phenotypic changes of IGF1R-deficient macrophages were investigated in culture. M\u03a6-IGF1R-KO significantly increased atherosclerotic lesion formation, as assessed by Oil Red O staining of en face aortas and aortic root cross-sections, and changed plaque composition to a less stable phenotype, characterized by increased macrophage and decreased \u03b1-smooth muscle actin\u2013positive cell population, fibrous cap thinning, and decreased collagen content. Brachiocephalic artery lesions of M\u03a6-IGF1R-KO mice had histological features implying plaque vulnerability. Macrophages isolated from M\u03a6-IGF1R-KO mice showed enhanced proinflammatory responses on stimulation by interferon-\u03b3 and oxidized low-density lipoprotein and elevated antioxidant gene expression levels. Moreover, IGF1R-deficient macrophages had decreased expression of ABCA1 and ABCG1 and reduced lipid efflux.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our data indicate that macrophage IGF1R signaling suppresses macrophage and foam cell accumulation in lesions and reduces plaque vulnerability, providing a novel mechanism whereby IGF-1 exerts antiatherogenic effects.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.116.021805","type":"journal-article","created":{"date-parts":[[2016,5,7]],"date-time":"2016-05-07T13:32:29Z","timestamp":1462627949000},"page":"2263-2278","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":111,"title":["Insulin-Like Growth Factor-1 Receptor Deficiency in Macrophages Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Apolipoprotein E\u2013Deficient Mice"],"prefix":"10.1161","volume":"133","author":[{"given":"Yusuke","family":"Higashi","sequence":"first","affiliation":[{"name":"From Departments of Medicine (Y.H., S.S., S.D., P.S., Z.L., P.D.) and Medical Pharmacology and Physiology (Y.H., S.S., M.W., D.W., H.Y., R.K.), University of Missouri School of Medicine, Columbia; and Department of Medicine, Tulane University School of Medicine, New Orleans, LA (S.-Y.S., R.T., P.L.-R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Sukhanov","sequence":"additional","affiliation":[{"name":"From Departments of Medicine (Y.H., S.S., S.D., P.S., Z.L., P.D.) and Medical Pharmacology and Physiology (Y.H., S.S., M.W., D.W., H.Y., R.K.), University of Missouri School of Medicine, Columbia; and Department of Medicine, Tulane University School of Medicine, New Orleans, LA (S.-Y.S., R.T., 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