Fig. 3.

Proposed pathway by which a change in environmental temperature leads to changes in collagen deposition in the trout heart. The change in cardiac composition that occurs with thermal acclimation is proposed to result from changes in the biomechanical forces experienced by the heart (A). For example, heart rate decreases at low temperature resulting in an increase in ventricle filling time, and as a result, an increase in stroke volume and a greater extension of the myocardium (Keen et al., 2017; Farrell, 1984). In addition, an acute decrease in environmental temperature causes an increase in blood viscosity, which in turn increases cardiac workload, and deformation of the myocardium cells (Farrell, 1984; Graham et al., 1985). Combined, these effects of low temperature are proposed to lead to an increase in the biomechanical stretch and shear stress experienced by the cardiomyocytes and fibroblasts that compose the myocardium (Keen et al., 2017) (B). Increased stretch of myocytes leads to the release of transforming growth factor β (TGF-β) (Katsumi et al., 2004; MacKenna et al., 1998) (C), while increased stretch of cardiac fibroblasts lead to the activation of mechanically sensitive proteins, and integrin proteins in the membrane (D) (Herum et al., 2017; MacKenna et al., 2000; Manso et al., 2009). This leads to the activation of G-coupled proteins and associated MAPK signaling proteins in the fibroblast (E) (Katsumi et al., 2004; Johnston and Gillis, 2020). Activated component proteins of the MAPK pathway in turn activate transcriptional factors that influence the expression of gene transcripts associated with the regulation of cardiac collagen (F) (Pramod and Shivakumar, 2014; Sinfield et al., 2013). Exposure of cardiac fibroblasts to TGF-β also causes increased activation (phosphorylation) of SMAD2 (G) (Visse and Nagase, 2003; Kolosova et al., 2011; Reed et al., 1994; Johnston and Gillis, 2018), another regulator of gene transcripts associated with collagen deposition, including col1A1. These changes in gene expression result in an increase in the expression and deposition of collagen in the extra cellular matrix (H) (Johnston and Gillis, 2017). Recent work also demonstrates that exposure of trout cardiac fibroblasts to microRNA 29b (miR-29b) leads to a decrease in the expression of col1A3 and in collagen type 1 content of the ECM (Johnston et al., 2019). These results suggest that regulation of collagen turnover by miRs could be involved in the removal of collagen from the heart (Johnston et al., 2019). It is not clear how the expression of miRs may be regulated by a temperature change.