{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:15:27Z","timestamp":1792631727308,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL115141,HL134849,HL148207,HL148355,HL153356"],"award-info":[{"award-number":["HL115141,HL134849,HL148207,HL148355,HL153356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["18SFRN33900144"],"award-info":[{"award-number":["18SFRN33900144"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["20SFRN35200163"],"award-info":[{"award-number":["20SFRN35200163"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,10]]},"abstract":"<jats:p>\n                    Patients with peripheral artery disease (PAD) and diabetes have the highest risk of critical limb ischemia (CLI) and amputation, yet the underlying mechanisms remain incompletely understood. MicroRNA (miRNA) sequencing of plasma from diabetic patients with or without CLI was compared to diabetic mice with acute or subacute limb ischemia to identify conserved miRNAs. miRNA-KO mice on high-fat diet were generated to explore the impact on CLI. Comparison of dysregulated miRNAs from diabetic individuals with PAD and diabetic mice with limb ischemia revealed conserved\n                    <jats:italic>miR-181<\/jats:italic>\n                    family members. High-fat\u2013fed, diabetic\n                    <jats:italic>Mir181a2b2<\/jats:italic>\n                    -KO mice had impaired revascularization in limbs due to abrogation of circulating Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes, with reduced accumulation in ischemic skeletal muscles. M2-like KO macrophages under diabetic conditions failed to produce proangiogenic cytokines. Single-cell transcriptomics of the bone marrow niche revealed that the reduced monocytosis in diabetic KO mice was a result of impaired hematopoiesis, with increased CXCR4 signaling in bone marrow Lineage\n                    <jats:sup>\u2013<\/jats:sup>\n                    Sca1\n                    <jats:sup>+<\/jats:sup>\n                    Kit\n                    <jats:sup>+<\/jats:sup>\n                    (LSK) cells. Exogenous Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes from nondiabetic KO mice rescued the impaired revascularization in ischemic limbs of diabetic KO mice. Increased\n                    <jats:italic>Cxcr4<\/jats:italic>\n                    expression was mediated by the miR-181 target,\n                    <jats:italic>Plac8<\/jats:italic>\n                    . Taken together, our results show that\n                    <jats:italic>MiR-181a\/b<\/jats:italic>\n                    is a putative mediator of diabetic CLI and contributes to changes in hematopoiesis, monocytosis, and macrophage polarization.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.163360","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T12:02:29Z","timestamp":1677153749000},"source":"Crossref","is-referenced-by-count":11,"title":["A miRNA\/CXCR4 signaling axis impairs monopoiesis and angiogenesis in diabetic critical limb ischemia"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-962X","authenticated-orcid":true,"given":"Henry S.","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Medicine, Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, 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