Right ventricular remodeling induced by prolonged excessive endurance exercise is mediated by upregulating Wnt/ß-catenin signaling in rats.

ABSTRACT

BACKGROUND: The aim of this study was to develop an animal model to investigate whether prolonged intensive endurance exercise induces RV remodeling, taking into account the involvement of Wnt/ß-catenin signaling. METHODS: Four-week-old male Wistar rats (100 to 125 g) were assigned to four groups (n = 8/group) 1) sixteen weeks of intensive (36 m/min) exercise (INT), 2) twelve weeks of the intensive exercise followed by four weeks of moderate intensity (18 m/min) exercise (INT + MOD), 3) twelve weeks of the intensive exercise followed by four weeks of detraining (INT + DT), and 4) sedentary rats (SED). The exercise protocols were performed five days a week for one h/day. Echocardiography, real-time PCR, western blotting, and histological staining were performed at the end of week sixteen. RESULTS: INT rats developed concentric hypertrophy without diastolic dysfunction compared to SED (p = 0.006) and INT + DT (p = 0.035). Wnt1, ß-catenin and CyclinD1 proteins in the training groups were significantly higher than SED rats (p < 0.001). Interestingly, INT rats had higher protein levels than INT + DT and INT + MOD (p < 0.001), with higher gene expression compared to SED rats (p < 0.05). There was also a significant increase in collagen deposition in INT rats compared to SED (p = 0.046) and INT + DT (p = 0.034). Furthermore, INT + MOD and INT + DT rats did not show any adverse structural, functional, or histological changes. CONCLUSIONS: Long-term intensive endurance training seems to be associated with increased collagen deposition and wall thickness in the RV through Wnt/ß-catenin signaling (which is concentration dependent), without changes in diastolic function. CLINICAL PERSPECTIVE Over the past decades, there has been an ongoing debate about whether the structural and functional adaptations of the cardiovascular system in trained endurance athletes are benign physiological responses to training or potentially pathological changes related to disease. While the adaptations of the left heart are well-documented, the remodeling of the right heart remains a subject of discussion. To gain insights into the ability of sustained high-intensity exercise to cause adverse right ventricular (RV) remodeling, we conducted an experimental study in which male rats were trained to run vigorously for 1 h daily over a 16-week period and compared them to a parallel group of sedentary control rats. Our findings revealed that intense long-term exercise induced morphological changes along with fibrosis affecting the RV. These fibrotic changes were a result of the 16-week vigorous exercise training regimen. If these results are confirmed in humans, they suggest that prolonged high-intensity endurance exercise training may lead to adverse cardiac remodeling. Our findings have important potential implications for the assessment of cardiac remodeling in individuals engaged in high-level exercise training.