Author:
Williams Erika,Chade Alejandro R.
Abstract
AbstractDespite advances in renovascular disease (RVD) research, gaps remain between experimental and clinical outcomes, translation of results, and the understanding of pathophysiological mechanisms. A predictive tool to indicate support (or lack of) for biological findings may aid clinical translation of therapies. We created a Boolean model of RVD and hypothesized that it would predict outcomes observed in our previous studies using a translational swine model of RVD. Our studies have focused on developing treatments to halt renal microvascular (MV) rarefaction in RVD, a major feature of renal injury. A network topology of 20 factors involved in renal MV rarefaction that allowed simulation of 5 previously tested treatments was created. Each factor was assigned a function based upon its interactions with other variables and assumed to be “on” or “off”. Simulations of interventions were performed until outcomes reached a steady state and analyzed to determine pathological processes that were activated, inactivated, or unchanged vs. RVD with no intervention. Boolean simulations mimicked the results of our previous studies, confirming the importance of MV integrity on treatment outcomes in RVD. Furthermore, our study supports the potential application of a mathematical tool to predict therapeutic feasibility, which may guide the design of future studies for RVD.
Funder
American Heart Association
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
U.S. Department of Health & Human Services | National Institutes of Health
Publisher
Springer Science and Business Media LLC
Reference68 articles.
1. Butler, D. Translational research: crossing the valley of death. Nature. 453, 840–842, https://doi.org/10.1038/453840a (2008).
2. Sung, N. S. et al. Central challenges facing the national clinical research enterprise. JAMA. 289, 1278–1287, https://doi.org/10.1001/jama.289.10.1278 (2003).
3. Genel, M. et al. 1995 Public Policy Plenary Symposium: “the crisis in clinical research”. Pediatr. Res. 39, 902–913, https://doi.org/10.1203/00006450-199605000-00027 (1996).
4. Veliz-Cuba, A. & Stigler, B. Boolean models can explain bistability in the lac operon. J. Comput. Biol. 18, 783–794, https://doi.org/10.1089/cmb.2011.0031 (2011).
5. Futrakul, N., Butthep, P. & Futrakul, P. Altered vascular homeostasis in chronic kidney disease. Clin. Hemorheol Microcir.c 38, 201–207 (2008).
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献