Key result
Comparative models reveal conserved cardiac remodeling pathways and endotherm-specific conditions promoting pathological phenotypes.
Why the study?
To explore how changes in hemodynamic load and cellular signaling pathways regulate cardiac remodeling across biomedical and comparative animal models, and to examine factors contributing to pathological phenotypes.
Comparative animal models reveal strong evolutionary conservation of the cellular signaling pathways regulating cardiac remodeling in response to hemodynamic load.
Pathway conservation across vertebrates supports further comparative studies; hypothesis-generating for endotherm pathology, should not yet change practice.
The ability of the vertebrate heart to remodel enables the cardiac phenotype to be responsive to changes in physiological conditions and aerobic demand. Examples include exercise-induced cardiac hypertrophy, and the significant remodeling of the trout heart during thermal acclimation. Such changes are thought to occur in response to a change in hemodynamic load (i.e. the forces that the heart must work against to circulate blood). Variations in hemodynamic load are caused by either a volume overload (high volume of blood returning to the heart, impairing contraction) or a pressure overload (elevated afterload pressure that the heart must contract against). The changes observed in the heart during remodeling are regulated by multiple cellular signaling pathways. The cardiac response to these regulatory mechanisms occurs across levels of biological organization, affecting cardiac morphology, tissue composition and contractile function. Importantly, prolonged exposure to pressure overload can cause a physiological response - that improves function - to transition to a pathological response that causes loss of function. This Review explores the role of changes in hemodynamic load in regulating the remodeling response, and considers the cellular signals responsible for regulating remodeling, incorporating knowledge gained from studying biomedical models and comparative animal models. We specifically focus on the renin-angiotensin system, and the role of nitric oxide, oxygen free radicals and transforming growth factor beta. Through this approach, we highlight the strong conservation of the regulatory pathways of cardiac remodeling, and the specific conditions within endotherms that may be conducive to the development of pathological phenotypes.
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Shaftoe et al. (2024) conducted a review in Cardiac remodeling. Comparative models of fish and mammals highlight the strong conservation of regulatory pathways in cardiac remodeling and specific conditions in endotherms conducive to pathological phenotypes.
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