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Peripheral arterial disease (PAD) is caused by atherosclerosis that results in ischemia mostly in the lower extremities. Clinical trials including VEGF-A administration for therapeutic angiogenesis have not been successful. The existence of anti-angiogenic isoform (VEGF<jats:sub>165b<\/jats:sub>) in PAD muscle tissues is a potential cause for the failure of therapeutic angiogenesis. Experimental measurements show that in PAD human muscle biopsies the VEGF<jats:sub>165b<\/jats:sub> isoform is at least as abundant if not greater than the VEGF<jats:sub>165a<\/jats:sub> isoform. We constructed three-compartment models describing VEGF isoforms and receptors, in human and mouse, to make predictions on the secretion rate of VEGF<jats:sub>165b<\/jats:sub> and the distribution of various isoforms throughout the body based on the experimental data. The computational results are consistent with the data showing that in PAD calf muscles secrete mostly VEGF<jats:sub>165b<\/jats:sub> over total VEGF. In the PAD calf compartment of human and mouse models, most VEGF<jats:sub>165a<\/jats:sub> and VEGF<jats:sub>165b<\/jats:sub> are bound to the extracellular matrix. VEGF receptors VEGFR1, VEGFR2 and Neuropilin-1 (NRP1) are mostly in \u2018Free State\u2019. This study provides a computational model of VEGF<jats:sub>165b<\/jats:sub> in PAD supported by experimental measurements of VEGF<jats:sub>165b<\/jats:sub> in human and mouse, which gives insight of VEGF<jats:sub>165b<\/jats:sub> in therapeutic angiogenesis and VEGF distribution in human and mouse PAD model.<\/jats:p>","DOI":"10.1038\/srep37030","type":"journal-article","created":{"date-parts":[[2016,11,17]],"date-time":"2016-11-17T12:58:38Z","timestamp":1479387518000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A multiscale computational model predicts distribution of anti-angiogenic isoform VEGF165b in peripheral arterial disease in human and mouse"],"prefix":"10.1038","volume":"6","author":[{"given":"Liang-Hui","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay Chaitanya","family":"Ganta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min H.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey D.","family":"Finley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian H.","family":"Annex","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksander S.","family":"Popel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,17]]},"reference":[{"key":"BFsrep37030_CR1","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1080\/10739680802095964","volume":"15","author":"F Mac Gabhann","year":"2008","unstructured":"Mac Gabhann, F. & Popel, A. 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