Cardiac allograft vasculopathy (CAV) is a coronary artery disease affecting 50% of heart transplant recipients, and it is the major cause of chronic graft rejection. CAV is driven by the interplay of immunological and non-immunological factors with the infiltration of macrophages as one of the main pathological triggers, setting off a cascade of events promoting endothelial damage and vascular cell dysfunction. Since etiology and evolution of the pathology are still largely unknown, disease management remains challenging and re-transplantation is today the only long-term solution to CAV. A deep understanding of the pathology mechanobiology is fundamental to improve prevention, diagnosis, and treatment of CAV. So far, in vivo models, mostly mouse-based, have been widely used to study CAV, but they are resource-consuming, pose many ethical issues, and allow limited time points of investigation during experimental follow-up. Recently, agent-based models (ABMs) proved to be valid computational tools for capturing and deciphering processes at cell/tissue level, augmenting cost-effectively in vivo lab-based experiments, i.e., guaranteeing richness in observation time points while maintaining low resource consumptions. We hypothesize that integrating ABMs with lab-based experiments can aid classic pre-clinical research by overcoming its limitations. Accordingly, we present a bidimensional ABM of CAV in a mouse-like coronary artery cross-section, simulating the arterial wall response to two distinct stimuli: inflammation and hemodynamic disturbances, the latter in terms of low wall-shear stress (WSS), which together trigger macrophage response activation and exacerbate vascular cell activities. In addition, we performed an extensive analysis to investigate the ABM working mechanisms and gain insight on the driving parameters and the stimuli influences. The ABM replicates with high fidelity a 4-week CAV initiation and progression, well highlighting lumen area decreasing due to progressive intimal thickening in regions exposed to high inflammation and low WSS. The sensitivity analysis remarked that the inflammatory-related events, rather than the WSS, predominantly drive CAV, corroborating the inflammatory nature of the vasculopathy. This proof-of-concept model offers to the scientific community an agile computational platform to deepen CAV understanding and to support the in vivo analysis of CAV in a cost-effective fashion.
Contributed talk session: CT02
Tuesday, July 18 at 2:30pm
Contributed talk session: CT02
CT02-CARD-1: CARD Subgroup Contributed Talks
- Elisa Serafini Houston Methodist Research Institute "An Agent-Based Model of Cardiac Allograft Vasculopathy: towards a Cost-Effective Platform to Better Understanding Chronic Rejection Dynamics"
- Pak-Wing Fok University of Delaware "Shear stress regulation in cylindrical arteries through medial growth and nitric oxide release"
- Shake Ibna Abir Western Kentucky University "Deep Learning Application of Long Short-Term Memory (LSTM) to predict the risk factors of etiology cardiovascular disease."
CT02-CDEV-1: CDEV Subgroup Contributed Talks
- Amanda M. Alexander University of Houston "Mathematical Models of Plasmid Partitioning and Loss in Dividing Cell Populations"
- Joseph Pollacco University of Oxford "Predicting the effects of antibiotics on the bacterial SOS response"
- Kieran Boniface University of Surrey "Mechanotransduction in organoid development"
CT02-ECOP-1: ECOP Subgroup Contributed Talks
- Alberto Tenore University Federico II of Naples, Italy "A model on phototrophic granular biofilms: microbial ecology and reactor performance"
- Alejandro Anderson University of Idaho "Contribution of waiting times therapies on mathematical models to tackle antimicrobial-drug resistance"
- Fordyce A. Davidson University of Dundee "Competitive outcome in biofilms: a race for space"
- Jessica Renz University of Bergen "Learning and predicting the pathways of AMR evolution with hypercubic inference"
CT02-ECOP-2: ECOP Subgroup Contributed Talks
- Aneequa Sundus Indiana University Bloomington "Investigating the potential for light-mediated spatial-temporal pattern formation in cyanobacteria mixed populations using agent-based modeling"
- Laura Wadkin Newcastle University "Mathematical and statistical modelling of the spread of tree diseases and invasive pests through forest environments"
- Suman Chakraborty Friedrich Schiller University Jena "Selection pressure by specialist and generalist insect herbivores leads to optimal constitutive plant defense. A mathematical model"
- Hong-Sung Jin Chonnam National University, Korea "Assessment of American Bullfrog spreading in Korea using cellular automata learning"
CT02-IMMU-1: IMMU Subgroup Contributed Talks
- Adquate Mhlanga Loyola University Chicago "Mathematical modeling of hepatitis D virus and hepatitis B virus interplay during anti-HDV treatment"
- Caroline I. Larkin University of Pittsburgh "Rule-based modeling of Eastern Equine Encephalitis Virus replication dynamics"
- Hayashi Rena Kyushu University "Establishment chance of a mutant strain decreases over time after infection with the original strain."
- Quintessa Hay Virginia Commonwealth University "A Mathematical Model for Wound Healing in Reef-Building Coral Pocillopora damicornis"
CT02-MEPI-1: MEPI Subgroup Contributed Talks
- Kiel Corkran University of Missouri- Kansas City "An Agent-Based modeling approach to Investigate Pandemic Preparedness of Nursing Homes"
- Sansao Pedro Eduardo Mondlane University "An Agent-Based Model for Studying the Spread of COVID-19 in Mozambique: Pandemic Planing Implications of Population Mobility Patterns"
- Theresa Sheets University of Utah "Forecasting SARS-CoV-2 Hospitalizations in Utah with Multiple Public Health Metrics"
CT02-MEPI-2: MEPI Subgroup Contributed Talks
- Chunyi Gai The University of British Columbia "Localized outbreaks in S-I-R model with diffusion"
- Keoni Castellano University of Nevada, Las Vegas "Dynamics of classical solutions of a multi-strain diffusive epidemic model"
- Laura F. Strube Virginia Tech "Appearance of Multistability and Hydra Effect in a Discrete-Time Epidemic Model with Ricker Growth"
- Neda Jalali University of Notre Dame "Impact of the interaction among DENV, ZIKV, and CHIKV on disease dynamics"
CT02-MFBM-1: MFBM Subgroup Contributed Talks
- Anna Konstorum Institute for Defense Analyses "A decomposition as a model: extracting mechanistic information from high-throughput time-course data using tensor dictionary learning"
- Dewayne A. Dixon Howard University "Core Epigenetic Module Biomarkers among Various PTSD Subtypes"
- Heber L Rocha Indiana University "Multiscale Modeling and Data Assimilation: A Path to Personalized Medicine"
- Hyun Kim Institute for basic science "Enhancing dimensionality reduction in single-cell RNA sequencing: a novel tool for improved preprocessing and noise filtering"
CT02-NEUR-1: NEUR Subgroup Contributed Talks
- Allison Cruikshank Duke University "Dynamical Questions in Volume Transmission"
- Gurpreet Jagdev Toronto Metropolitan University "The interplay between asymmetric noise and uneven coupling of two coupled neuronal oscillators"
- Marina Chugunova University of Waterloo, Canada "Modelling duality of the exocytosis initiation in GnRH neurons"
- Zhuo-Cheng Xiao New York University "Efficient models of the cortex via coarse-grained interactions and local response functions"
CT02-ONCO-1: ONCO Subgroup Contributed Talks
- David Basanta Moffitt Cancer Center "Using game theory to model somatic evolution in cancer treated in the presence of environmentally mediated protection"
- Stefano Casarin Houston Methodist Research Institute "Improving the Efficacy of Radium223 for Prostate Cancer Bone Metastasis through Targeting β1 Integrin: In Silico Modeling and In Vivo Validation"
- Tatiana Miti H. Lee Moffitt Cancer Center "Integrating Spatatial statistics and ABMs to Study Stromal Effects on the Remission-Relapse Dynamics of NSCLC and TNBC"
- Zuping Wang University of Maryland, College Park "A mathematical model of TCR T cell therapy for cervical cancer"