Myocardial Fibrosis: Cell Signaling and In Vitro Modeling

Caleb Graham; Palaniappan Sethu

doi:10.1007/978-3-031-08309-9_10

Myocardial Fibrosis: Cell Signaling and In Vitro Modeling

Review

In: Cardiovascular Signaling in Health and Disease [Internet]. Cham (CH): Springer; 2022.

2022 Sep 21.

Authors

Caleb Graham^{1

2}, Palaniappan Sethu^{1

2}

Book Editors

Narasimham L. Parinandi¹, Thomas J. Hund²

Affiliations

¹ Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
² Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA

Book Affiliations

¹ Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA
² Departments of Biomedical Engineering and Internal Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA

Excerpt

Heart disease is the leading cause of death in the US and worldwide. In addition to alterations in cardiomyocyte structure and cellular composition, the adverse ventricular remodeling seen post-myocardial infarction, in various types of cardiomyopathies, and in response to pressure and volume overload usually includes myocardial fibrosis. This condition is characterized by the deposition of excess extracellular matrix (ECM) proteins and often begins as an adaptive response to injury or hemodynamic stress, but then persists and transitions into a pathological process. Presence and amount of fibrosis have proven to be reliable negative prognostic indicators in the setting of heart failure, and there is mounting evidence to suggest that fibrosis directly worsens disease outcomes. While 2D cell monoculture experiments have proven invaluable in understanding some of the triggers and signaling dynamics involved in the development of myocardial fibrosis and its downstream effects, these disease models do not accurately recapitulate pathophysiological remodeling seen in the in vivo setting. Despite advances in the development of 3D cell culture and tissue engineering techniques over the past few decades, as well as the discovery and utilization of induced pluripotent stem cells, this complex pathological process has proven difficult to faithfully model in vitro. This complex and dynamic process of fibrotic remodeling relies on a multitude of cellular and extracellular signals originating from within the myocardium and from systemic interactions with the immune and endocrine systems. The goal of this chapter is to provide an understanding of fibrosis in the context of the myocardium, detail efforts to model myocardial fibrosis in vitro, discuss limitations of available in vitro models and, finally, highlight how in vitro models have made critical contributions to our understanding of this condition by elucidating cell-cell and cell-ECM interactions and signaling pathways involved in its development.

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