Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis PMID: 33839725

Target-related Cytokines

2026-09-23

Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis

J Vasc Res. 2021;58(4):207-230. doi: 10.1159/000514211.

Mark Lagatuz ¹ , Ruchi J Vyas ² , Marina Predovic ³ , Shiyin Lim ³ , Nicole Jacobs ³ , Miguel Martinho ⁴ , Hamed Valizadegan ⁴ , David Kao ⁵ , Nikunj Oza ⁵ , Corey A Theriot ⁶ ⁷ , Susana B Zanello ⁷ , Giovanni Taibbi ⁸ , Gianmarco Vizzeri ⁸ , Mariana Dupont ⁹ , Maria B Grant ⁹ , Daniel J Lindner ¹⁰ , Hans-Christian Reinecker ¹¹ , Alexander Pinhas ¹² , Toco Y Chui ¹² , Richard B Rosen ¹² ¹³ , Nicanor Moldovan ¹⁴ ¹⁵ , Mary B Vickerman ¹⁶ , Krishnan Radhakrishnan ¹⁷ ¹⁸ , Patricia Parsons-Wingerter ¹⁹ ²⁰

Affiliations

1. Redline Performance Solutions, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
2. Mori Associates, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
3. Blue Marble Space Institute of Science, Space Biology Division, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
4. Universities Space Research Association, Intelligent Systems Division, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
5. Advanced Supercomputing & Intelligent Systems Divisions, Exploration Technology Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
6. Department of Preventive Medicine and Community Health, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
7. KBRWyle, Johnson Space Center, National Aeronautics and Space Administration, Houston, Texas, USA.
8. Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
9. Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama, Birmingham, Alabama, USA.
10. Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
11. Departments of Medicine and Immunology, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
12. Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA.
13. Icahn School of Medicine at Mount Sinai, New York, New York, USA.
14. Department of Ophthalmology, Indiana University School of Medicine and Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA.
15. Richard L. Roudebush VA Medical Center, Veteran's Administration, Indianapolis, Indiana, USA.
16. Data Systems Branch, John Glenn Research Center, National Aeronautics and Space Administration, Cleveland, Ohio, USA.
17. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, U.S. Department of Health and Human Services, Rockville, Maryland, USA.
18. College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
19. Space Biology Division, Space Technology Mission Directorate, Ames Research Center, National Aeronautics and Space Administration, Moffett Field, California, USA.
20. Low Gravity Exploration Technology, Research and Engineering Directorate, John Glenn Research Center, National Aeronautics and Space Administration, Cleveland, Ohio, USA.

Abstract

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and Cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic Fibroblast Growth Factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D Bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic Retinopathy, and venous occlusive disease.

Keywords

3D bioprinting; Angiogenesis; Central retinal vein occlusion; Diabetic retinopathy; Keratinocyte growth factor; Leronlimab; Microvascular; Saccharomyces boulardii; Spaceflight-Associated Neuro-ocular Syndrome.