The passive mechanical properties of the vertebrate heart are controlled in part by the composition of the extracellular matrix (ECM). Changes in the ECM, caused by increased blood pressure, injury or disease can affect the capacity of the heart to fill with blood during diastole. In mammalian species, cardiac fibrosis caused by an increase in collagen in the ECM, leads to a loss of heart function and these changes in composition are considered to be permanent. Recent work has demonstrated that the cardiac ventricle of some fish species have the capacity to both increase and decrease collagen content in response to thermal acclimation. It is thought that these changes in collagen content help maintain ventricle function over seasonal changes in environmental temperatures. This current work reviews the cellular mechanisms responsible for regulating collagen deposition in the mammalian heart and proposes a cellular pathway by which a change in temperature can affect the collagen content of the fish ventricle through mechanotransduction. This work specifically focuses on the role of transforming growth factor β1, MAPK signaling pathways, and biomechanical stretch in regulating collagen content in the fish ventricle. It is hoped that this work increases the appreciation of the use of comparative models to gain insight into phenomenon with biomedical relevance.