{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:57:46Z","timestamp":1785236266977,"version":"3.55.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Peripheral artery disease is caused by atherosclerotic occlusion of vessels outside the heart and most commonly affects vessels of the lower extremities. Angiogenesis is a part of the postischemic adaptation involved in restoring blood flow in peripheral artery disease. Previously, in a murine hind limb ischemia model of peripheral artery disease, we identified ADAM12 (a disintegrin and metalloproteinase gene 12) as a key genetic modifier of postischemic perfusion recovery. However, less is known about ADAM12 regulation in ischemia. MicroRNAs are a class of small, noncoding, single\u2010stranded RNAs that regulate gene expression primarily through transcriptional repression of messenger RNA (mRNA). We showed microRNA\u201029a (miR\u201029a) modulates ADAM12 expression in the setting of diabetes and ischemia. However, how miR\u201029a modulates ADAM12 is not known. Moreover, the physiological effects of miR\u201029a modulation in a nondiabetic setting is not known.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We overexpressed or inhibited miR\u201029a in ischemic mouse gastrocnemius and tibialis anterior muscles, and quantified the effect on perfusion recovery, ADAM12 expression, angiogenesis, and skeletal muscle regeneration. In addition, using RNA immunoprecipitation\u2013based anti\u2010miR competitive assay, we investigated the interaction of miR\u201029a and ADAM12 mRNA in mouse microvascular endothelial cell, skeletal muscle, and human endothelial cell lysates. Ectopic expression of miR\u201029a in ischemic mouse hind limbs decreased ADAM12 mRNA expression, increased skeletal muscle injury, decreased skeletal muscle function, and decreased angiogenesis and perfusion recovery, with no effect on skeletal muscle regeneration and myofiber cross\u2010sectional area following hind limb ischemia. RNA immunoprecipitation\u2013based anti\u2010miR competitive assay studies showed miR\u201029a antagomir displaced miR\u201029a and ADAM12 mRNA from the AGO\u20102 (Argonaut\u20102) complex in a dose dependent manner.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Taken together, the data show miR\u201029a suppresses ADAM12 expression by directly binding to its mRNA, resulting in impaired skeletal muscle function, angiogenesis, and poor perfusion. Hence, elevated levels of miR\u201029a, as seen in diabetes and aging, likely contribute to vascular pathology, and modulation of miR\u201029a could be a therapeutic target.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025727","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:38:16Z","timestamp":1660124296000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["microRNA\u201029a Regulates ADAM12 Through Direct Interaction With ADAM12 mRNA and Modulates Postischemic Perfusion Recovery"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-7438","authenticated-orcid":false,"given":"Victor","family":"Lamin","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0751-5683","authenticated-orcid":false,"given":"Joseph","family":"Verry","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumayowa S.","family":"Dokun","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Carver College of Medicine University of Iowa Iowa City IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Kronemberger","sequence":"additional","affiliation":[{"name":"Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine University of Iowa Iowa City IA"},{"name":"Department of Health and Human Physiology, College of Liberal Arts and Sciences University of Iowa Iowa City 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