{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:02:27Z","timestamp":1790834547502,"version":"4.1.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"763","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,9,4]]},"abstract":"<jats:p>\n            Diabetic vascular disease is a major complication of diabetes mellitus (DM). Chemokine C-C motif ligand 7 (CCL7) attracts macrophages and monocytes, amplifying inflammatory processes in the vasculature. We hypothesized a causal role for CCL7 in diabetic vasculopathy. CCL7 concentrations were higher in the plasma of patients with type 2 DM, as well as in supernatants from their endothelial progenitor cells (EPCs). High-glucose stimulation increased the secretion of CCL7 from human dermal microvascular endothelial cells (HDMECs) through the c-Fos and c-Jun signaling pathways. CCL7 inhibition using knockdown or neutralization antibody treatment reversed the high glucose\u2013induced impaired tube formation and migration abilities of EPCs, human aortic endothelial cells, human coronary artery endothelial cells, and HDMECs. Administration of recombinant human CCL7 protein impaired tube formation and migration abilities by down-regulating the AKT\u2013endothelial nitric oxide synthase and AKT\/nuclear factor erythroid 2\u2013related factor 2\/heme oxygenase\u20131\/vascular endothelial growth factor\/stromal cell\u2013derived factor\u20131 pathways and by up-regulating ERK\/phosphorylated p65\/interleukin-1\u03b2\/interleukin-6\/tumor necrosis factor\u2013\u03b1 pathways through CC chemokine receptor 3 in endothelial cells.\n            <jats:italic>Ccl7<\/jats:italic>\n            knockout in streptozotocin-treated mice showed improved neovasculogenesis in ischemic limbs and accelerated wound repair, with increased circulating EPCs and capillary density. CCL7 antibody treatment in\n            <jats:italic>db\/db<\/jats:italic>\n            mice and high-fat diet\u2013induced hyperglycemia mice showed improved neovasculogenesis in ischemic limbs and wound areas, accompanied by up-regulation of angiogenic proteins and down-regulation of inflammatory proteins. Endothelial cell\u2013specific\n            <jats:italic>Ccl7<\/jats:italic>\n            -knockout mice showed ameliorated diabetic vasculopathy in streptozotocin-induced DM. This study highlights the potential of CCL7 as a therapeutic target for diabetic vasculopathy.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adn1507","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T17:59:54Z","timestamp":1725472794000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of CCL7 improves endothelial dysfunction and vasculopathy in mouse models of diabetes mellitus"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-7029","authenticated-orcid":true,"given":"Ting-Ting","family":"Chang","sequence":"first","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Wei","family":"Mo","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4776-5639","authenticated-orcid":true,"given":"Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-790X","authenticated-orcid":true,"given":"Liang-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan."},{"name":"Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, 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