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Cardiac pathologies emerging from collective cellular behavior: a study of cardiac fibrosis in vitro and in silico

Teresa Abney (), Kenneth Pryse (), Ali Nekouzadeh (), ShengLin Lee (), William McConnaughey (), Elliot Elson (), Guy Genin (Washington University)

Mechanics of cell sheets, multicellular assemblies and tissues

Mon 10:45 - 12:15

Barus-Holley 141

Hypertension is one of the leading causes of death in the Western world. The pathology involves what appears to be an initially adaptive response to prolonged hypertension, in which cardiac fibroblasts within the heart convert to myofibroblasts, a larger, contractile phenotype. We developed an in vitro model to identify how varying concentrations and distributions of myofibroblasts affect the contractile function of heart muscle. Myofibroblasts produce fibrous connective tissue that stiffens heart muscle. We show experimentally and through mathematical models that this can improve the contraction of heart muscle. Myofibroblasts also disrupt normal patterns of electrical excitation of cardiomyocytes, potentially leading to heart failure through one of several pathways. Electrophysiologic measurement and modeling, combined with mechanical measurement and modeling, suggests that diffuse fibrosis is beneficial to the contractile function of heart tissue, but that collective effects from interactions between cells lead to cessation of contractile function. Results further motivate mechanical interventions that might offer hope for limiting the spread of myofibroblasts.