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

Liang Hui Chu, Vijay Chaitanya Ganta, Min H. Choi, George Chen, Stacey D. Finley, Brian H. Annex, Aleksander S Popel

Research output: Contribution to journalArticle

Abstract

Angiogenesis is the growth of new blood vessels from pre-existing microvessels. 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 (VEGF165b) in PAD muscle tissues is a potential cause for the failure of therapeutic angiogenesis. Experimental measurements show that in PAD human muscle biopsies the VEGF165b isoform is at least as abundant if not greater than the VEGF165a isoform. We constructed three-compartment models describing VEGF isoforms and receptors, in human and mouse, to make predictions on the secretion rate of VEGF165b 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 VEGF165b over total VEGF. In the PAD calf compartment of human and mouse models, most VEGF165a and VEGF165b are bound to the extracellular matrix. VEGF receptors VEGFR1, VEGFR2 and Neuropilin-1 (NRP1) are mostly in â Free State'. This study provides a computational model of VEGF165b in PAD supported by experimental measurements of VEGF165b in human and mouse, which gives insight of VEGF165b in therapeutic angiogenesis and VEGF distribution in human and mouse PAD model.

Original languageEnglish (US)
Article number37030
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 17 2016

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Peripheral Arterial Disease
Protein Isoforms
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor
Muscles
Neuropilin-1
Microvessels
Extracellular Matrix
Blood Vessels
Lower Extremity
Atherosclerosis
Therapeutics
Ischemia
Clinical Trials
Biopsy
Growth

ASJC Scopus subject areas

  • General

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A multiscale computational model predicts distribution of anti-angiogenic isoform VEGF165b in peripheral arterial disease in human and mouse. / Chu, Liang Hui; Ganta, Vijay Chaitanya; Choi, Min H.; Chen, George; Finley, Stacey D.; Annex, Brian H.; Popel, Aleksander S.

In: Scientific Reports, Vol. 6, 37030, 17.11.2016.

Research output: Contribution to journalArticle

Chu, Liang Hui ; Ganta, Vijay Chaitanya ; Choi, Min H. ; Chen, George ; Finley, Stacey D. ; Annex, Brian H. ; Popel, Aleksander S. / A multiscale computational model predicts distribution of anti-angiogenic isoform VEGF165b in peripheral arterial disease in human and mouse. In: Scientific Reports. 2016 ; Vol. 6.
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