MS03 - CARD-1
Barbie Tootle Room (#3156) in The Ohio Union

Integrating Mathematics Across the Cardiovascular System: A Mini-Symposium on Multilevel Modelling of Cardiovascular Biology

Tuesday, July 18 at 10:30am

SMB2023 SMB2023 Follow Tuesday during the "MS03" time block.
Room assignment: Barbie Tootle Room (#3156) in The Ohio Union.
Note: this minisymposia has multiple sessions. The other session is MS04-CARD-1 (click here).

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Jessica Crawshaw, Vijay Rajagopal, Michael Watson, Mitchel Colebank, Seth Weinberg


Cardiovascular biology is a complex and multifaceted field that encompasses a wide range of physical and biological processes occurring across multiple levels, including the cardiac, vascular, and microvascular systems. At each level of the cardiovascular system, mathematical modelling plays a critical role in integrating data and understanding the underlying mechanisms governing these processes. While there has been significant progress in mathematical and computational cardiovascular biology over the past decade, mathematicians and engineers at each level have tended to work in isolated silos, which risks producing a fragmented understanding of the cardiovascular system and threatens to slow scientific progress. This issue carries significant implications for the broader field of mathematical biology, as cardiovascular models frequently serve as building blocks for larger models of other systems, such as developmental biology, oncology, drug development, tissue engineering, and regenerative medicine. To address this challenge, this mini-symposium seeks to provide a forum for collaboration between mathematicians and engineers from each level of the cardiovascular system. The aim is to facilitate the exchange of ideas, foster new collaborations, and promote a more comprehensive understanding of cardiovascular biology through mathematical modelling. The mini-symposium will feature talks by leading researchers in the field covering various topics, including cardiac physiology modelling, vascular disease, microvascular development, and blood flow dynamics. Each talk will showcase innovative mathematical models and computational tools used to understand the complex processes underlying cardiovascular development, function, and dysfunction. This mini-symposium provides a unique opportunity for mathematicians and engineers interested in cardiovascular biology to exchange ideas, discuss recent developments, and foster new collaborations.

Miguel Bernabeu

The University of Edinburgh (The Bayes Centre)
"Red blood cell dynamics in complex vascular networks: implications in development and disease"
In this talk, I will review recent progress on the application of cellular flow simulations (with the HemeLB flow solver) to characterise red blood cell (RBC) dynamics in complex vascular networks. First, I will demonstrate an intriguing association between reduced RBC flow and vascular remodelling during vascular development. Second, I will present two recently published studies relating vascular phenotypes encountered in the tumour microenvironment with anomalous RBC transport and potential tumour tissue hypoxia, a mechanism previously unreported. Finally, I will outline future research directions related to predicting vascular network function from its structure and how this can become a tool for biomedical investigation and eventually clinical translation.

Mette Olufsen

North Carolina State University (Mathematics)
"Multiscale approach for assessment of hemodynamics in Pulmonary Hypertension"
This study discusses the use of multiscale models for the assessment of pulmonary hypertension (PH). This heterogeneous disease with multiple subtypes is categorized as pre-capillary (leading to remodeling of the pulmonary arteries), or post-capillary, also referred to as venous PH. The latter is often associated with left heart failure. Common for both types is an increase in pulmonary arterial pressure. This study will use 1D and systems-level modeling to assess changes and propose treatments for PH patients. The focus is on patient-specific predictions using a computational framework merging imaging and dynamic data with computational models. The systems-level model allows us to study the effects of high pulmonary arterial pressure on the cardiovascular system as a whole, particularly how a right heart disease can affect the left heart via ventricular-ventricular interaction. Whereas the spatial pulmonary network model can help predict lung perfusion. Both properties are essential to assess patient health. We extract pulmonary networks represented by a directed graph extracted from computed tomography images. In the large vessels, we solve the 1D Navier Stokes equations. In contrast, in the systems level model and the network of small vessels and capillaries, we solve linearized equations coupled to large vessels via outflow boundary conditions. We demonstrate the importance of sensitivity analysis and parameter inference to render the model patient-specific and show how the calibrated models can be used to predict treatment effects for patients with thromboembolic pulmonary hypertension.

Fabian Spill

University of Birmingham (Mathematics)
"The Human Cardiac Age-OME: Multi-omics analysis and mechanistic modelling of the ageing heart"
The heart is a mechanical pump, whose function is essential to life. Reduced heart function in ageing is a key contributor to frailty, and heart diseases are among the major causes of death. An impediment to understanding age-related heart diseases is our lack of understanding of healthy cardiac ageing. This limits our ability to distinguish data from age-related diseases to data from healthily aged hearts, identifying the true causes of these diseases. A challenge to understanding healthy ageing is a lack of available data from healthy donors. Making use of the unique resources of the Sydney Heart Bank, we present an integrated mathematical modelling and bioinformatics analysis of human cardiac ageing. We performed transcriptomics, proteomics, metabolomics, and lipidomics analysis, and obtained a holistic picture of metabolic and mechanical alterations that characterize the ageing heart. In older hearts, we observed a downregulation of proteins involved in calcium signalling and of the contractile apparatus itself. In addition, we found a potential counteractive upregulation of central carbon generation of fuel, upregulation of glycolysis and increases in long-chain fatty acids. We then developed predictive mechanistic models that demonstrated how calcium signalling and oxidative phosphorylation, two key pathways regulating cardiomyocyte function, are altered in the ageing heart.
Additional authors: Cassandra Malecki, University of Sydney; Giovanni Guglielmi, University of Melbourne Vijay Rajagopal, University of Melbourne John F. O’Sullivan, University of Sydney Sean Lal, University of Sydney

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Annual Meeting for the Society for Mathematical Biology, 2023.