Cold-induced fibrosis and metabolic remodeling in the turtle (Trachemys scripta) ventricle.

AIM: Cardiac fibrosis contributes to systolic and diastolic dysfunction and can disrupt electrical pathways in the heart. There are currently no therapies that prevent or reverse fibrosis in human cardiac disease. However, animals like freshwater turtles undergo seasonal remodeling of their hearts, demonstrating the plasticity of fibrotic remodeling. In Trachemys scripta, cold temperature affects cardiac load, suppresses metabolism, and triggers a cardiac remodeling response that includes fibrosis. METHODS: We investigated this remodeling using Fourier transform infrared (FTIR) imaging spectroscopy, together with functional assessment of muscle stiffness, and molecular, histological, and enzymatic analyses in control (25°C) T. scripta and after 8 weeks of cold (5°C) acclimation. RESULTS: FTIR revealed an increase in absorption bands characteristic of protein, glycogen, and collagen following cold acclimation, with a corresponding decrease in bands characteristic of lipids and phosphates. Histology confirmed these responses. Functionally, micromechanical stiffness of the ventricle increased following cold exposure assessed via atomic force microscopy (AFM) and was associated with decreased activity of regulatory matrix metalloproteinases (MMPs) and increased expression of MMP inhibitors (TMPs) which regulate collagen deposition. CONCLUSIONS: By defining the structural and metabolic underpinnings of the cold-induced remodeling response in the turtle heart, we show commonalities between metabolic and fibrotic triggers of pathological remodeling in human cardiac disease. We propose the turtle ventricle as a novel model for studying the mechanisms underlying fibrotic and metabolic cardiac remodeling.