A multiscale computational model predicts distribution of anti-angiogenic isoform VEGF165b in peripheral arterial disease in human and mouse

• DOI: 10.1038/srep37030
• Publication Date: 2016-11-17T12:58:38Z
• Authors: Liang-Hui Chu; Vijay Chaitanya G...; Min H. Choi; George Chen; Stacey D. Finley; Brian H. Annex; Aleksander S. Popel
• Keywords: Human disease

Angiogenesis is the growth of new blood vessels from pre-existing microvessels. Peripheral arterial disease (PAD) caused by atherosclerosis that results in ischemia mostly lower extremities. Clinical trials including VEGF-A administration for therapeutic angiogenesis have not been successful. The existence anti-angiogenic isoform (VEGF165b) PAD muscle tissues a potential cause failure angiogenesis. Experimental measurements show human biopsies VEGF165b at least as abundant if greater than VEGF165a isoform. We constructed three-compartment models describing VEGF isoforms and receptors, mouse, to make predictions on secretion rate distribution various throughout body based experimental data. computational are consistent with data showing calf muscles secrete over total VEGF. In compartment mouse models, most bound extracellular matrix. receptors VEGFR1, VEGFR2 Neuropilin-1 (NRP1) 'Free State'. This study provides model supported which gives insight model.