{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:16:05Z","timestamp":1792631765669,"version":"4.5.0"},"reference-count":86,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,4,4]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6\u2010phosphofructo\u20102\u2010kinase\/fructose\u20102,6\u2010biphosphatase, isoform\u20103), is the major metabolic pathway for ATP generation. In preclinical peripheral artery disease models, VEGF\n              <jats:sub>165<\/jats:sub>\n              a (vascular endothelial growth factor\n              <jats:sub>165<\/jats:sub>\n              a) and microRNA\u201093 both promote angiogenesis.\n            <\/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\">\n              Mice following hind\u2010limb ischemia (HLI) and ECs with, and without, hypoxia and serum starvation were examined with, and without, microRNA\u201093 and VEGF\n              <jats:sub>165<\/jats:sub>\n              a. Post\u2010HLI perfusion recovery was monitored. EC metabolism was studied using seahorse assay, and the expression and activity of major metabolism genes were assessed. Reactive oxygen species levels and EC permeability were evaluated. C57Bl\/6J mice generated a robust angiogenic response to HLI, with ECs from ischemic versus nonischemic muscle demonstrating no increase in glycolysis. Balb\/CJ mice generated a poor angiogenic response post\u2010HLI; ischemic versus nonischemic ECs demonstrated significant increase in glycolysis. MicroRNA\u201093\u2010treated Balb\/CJ mice post\u2010HLI showed better perfusion recovery, with ischemic versus nonischemic ECs showing no increase in glycolysis. VEGF\n              <jats:sub>165<\/jats:sub>\n              a\u2010treated Balb\/CJ mice post\u2010HLI showed no improvement in perfusion recovery with ischemic versus nonischemic ECs showing significant increase in glycolysis. ECs under hypoxia and serum starvation upregulated PFKFB3. In ECs under hypoxia and serum starvation, VEGF\n              <jats:sub>165<\/jats:sub>\n              a versus control significantly upregulated PFKFB3 and glycolysis, whereas miR\u201093 versus control demonstrated no increase in PFKFB3 or glycolysis. MicroRNA\u201093 versus VEGF\n              <jats:sub>165<\/jats:sub>\n              a upregulated glucose\u20106\u2010phosphate dehydrogenase expression and activity, activating the pentose phosphate pathway. MicroRNA\u201093 versus control increased reduced nicotinamide adenine dinucleotide phosphate and virtually eliminated the increase in reactive oxygen species. In ECs under hypoxia and serum starvation, VEGF\n              <jats:sub>165<\/jats:sub>\n              a significantly increased and miR\u201093 decreased EC permeability.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In peripheral artery disease, activation of the pentose phosphate pathway to promote angiogenesis may offer potential therapeutic advantages.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027986","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T09:24:22Z","timestamp":1679995462000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Pentose Pathway Activation Is Superior to Increased Glycolysis for Therapeutic Angiogenesis in Peripheral Arterial Disease"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2919-5329","authenticated-orcid":false,"given":"Abdelrahman A.","family":"Zaied","sequence":"first","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"},{"name":"Department of Medicine Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-2381","authenticated-orcid":false,"given":"Masuko","family":"Ushio\u2010Fukai","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-571X","authenticated-orcid":false,"given":"Tohru","family":"Fukai","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Toxicology Medical College of Georgia at Augusta University Augusta GA USA"},{"name":"Charlie Norwood Veterans Affairs Medical Center Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Kovacs\u2010Kasa","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-4632","authenticated-orcid":false,"given":"Suhib","family":"Alhusban","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-0097","authenticated-orcid":false,"given":"Varadarajan","family":"Sudhahar","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-8320","authenticated-orcid":false,"given":"Vijay C.","family":"Ganta","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-8243","authenticated-orcid":false,"given":"Brian H.","family":"Annex","sequence":"additional","affiliation":[{"name":"Vascular Biology Center Medical College of Georgia at Augusta University Augusta GA USA"},{"name":"Department of Medicine Medical College of Georgia at Augusta University Augusta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.037"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.010"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48676-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21121756"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002748"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2016.11.003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318805"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318266"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000093398.16124.29"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(03)00102-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1522-1865(02)00158-0"},{"key":"e_1_3_2_13_2","first-page":"1667","article-title":"Mouse model of angiogenesis","volume":"152","author":"Couffinhal T","year":"1998","unstructured":"Couffinhal T, Silver M, Zheng LP, Kearney M, Witzenbichler B, Isner JM. 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