Exercise intensity-dependent cardiac telocyte expansion is associated with physiological growth despite JAK/STAT...

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.