Exercise intensity-dependent cardiac telocyte expansion is associated with physiological growth despite JAK/STAT pathway inactivity in male Wistar rats.

While exercise induces physiological cardiac growth, the underlying cellular mechanisms remain incompletely understood. This study investigated the role of cardiac telocytes (TCs) and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in mediating exercise intensity-dependent cardiac adaptation. Twenty-four male Wistar rats were assigned to control (CTRL), high-intensity interval training (HIIT) or low-intensity interval training (LIIT) groups for 8 weeks. Physiological hypertrophy was assessed via heart weight/body weight ratio, left ventricular wall thickness, cardiomyocyte size and number. Cardiac TCs were quantified by immunofluorescence (CD34-platelet-derived growth factor receptor (PDGFR)-α/β). Gene expression of IL-6, cardiotrophin-1 (CTF1), GP130, JAK2, STAT3 and GATA4 was analysed by qPCR, and interleukin (IL)-6 protein levels were measured by ELISA. Both HIIT and LIIT robustly induced physiological cardiac hypertrophy and cardiomyogenesis, with HIIT producing a significantly greater response. This was accompanied by a significant, intensity-dependent expansion of the cardiac TC population in both HIIT and LIIT groups compared to CTRL, with HIIT inducing a greater increase than LIIT (P < 0.001). Furthermore, GATA4 expression, a marker of cardiac stem cell activation, was significantly upregulated in both trained groups. While cardiac IL-6 gene expression and protein levels were elevated, particularly after HIIT (P = 0.003), the core components of the JAK/STAT pathway (GP130, JAK2, STAT3) remained transcriptionally unaltered. Our findings establish cardiac TCs as novel, intensity-sensing cellular mediators of exercise-induced physiological growth. The adaptive process, linked to stem cell activation, occurs without concomitant transcriptional upregulation of the core JAK/STAT signalling pathway components, suggesting the involvement of alternative, potentially non-canonical, mechanistic pathways. This highlights the TC-cardiac stem cell axis as a potential target for optimizing exercise regimens for cardiac repair.