title: The Vital Role of Blood Flow-Induced Proliferation and Migration in Capillary Network Formation in a Multiscale Model of Angiogenesis.
abstract: Sprouting angiogenesis and capillary network formation are tissue scale phenomena. There are also sub-scale phenomena involved in angiogenesis including at the cellular and intracellular (molecular) scales. In this work, a multiscale model of angiogenesis spanning intracellular, cellular, and tissue scales is developed in detail. The key events that are considered at the tissue scale are formation of closed flow path (that is called loop in this article) and blood flow initiation in the loop. At the cellular scale, growth, migration, and anastomosis of endothelial cells (ECs) are important. At the intracellular scale, cell phenotype determination as well as alteration due to blood flow is included, having pivotal roles in the model. The main feature of the model is to obtain the physical behavior of a closed loop at the tissue scale, relying on the events at the cellular and intracellular scales, and not by imposing physical behavior upon it. Results show that, when blood flow is considered in the loop, the anastomosed sprouts stabilize and elongate. By contrast, when the loop is modeled without consideration of blood flow, the loop collapses. The results obtained in this work show that proper determination of EC phenotype is the key for its survival.
authors.affiliation: Department of Mechanical Engineering, K. N. T. University of Technology, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Bazmara
authors.affiliation: Department of Mechanical Engineering, K. N. T. University of Technology, Tehran, Iran; Division of Nuclear Medicine, Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, United States of America.
authors.forename: Madjid
authors.initials: M
authors.lastname: Soltani
authors.affiliation: Department of Mechanical Engineering, K. N. T. University of Technology, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Sefidgar
authors.affiliation: Department of Mechanical Engineering, K. N. T. University of Technology, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Bazargan
authors.affiliation: Department of Mechanical Engineering, K. N. T. University of Technology, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Mousavi Naeenian
authors.affiliation: Division of Nuclear Medicine, Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD, United States of America.
authors.forename: Arman
authors.initials: A
authors.lastname: Rahmim
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D042501:Angiogenic Proteins