Circulating Gal‐3 and sST2 are associated with acute exercise‐induced sustained endothelial activation: Possible relevance for fibrosis development?

Abstract

Long‐term, intense endurance exercise training can occasionally induce endothelial micro‐damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well‐trained male participants (10 runners and 10 cyclists) performed a strenuous high‐intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal‐3 and sST2 concentrations were investigated by enzyme‐linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal‐3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal‐3 and sST2 concentrations both showed a positive relationship with ECs (rrm = 0.68, P = 0.001 and rrm = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal‐3 was significant only in cyclists, but equally strong for both modalities. Gal‐3 was also related to exercise‐induced CTi (rrm = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise‐released Gal‐3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise‐induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long‐term pathological endothelial adaptation should be investigated further, also relative to the exercise modality.New Findings What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal‐3 is an enhanced cardiac contractility. Acute exercise‐released Gal‐3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

Galectin‐3 and suppression of tumorigenicity 2: Two emerging cardiac biomarkers that may be predictors of cardiac fibrosis development in sport

“…It is unknown if sustained, frequent, intense exercise can cause fibrosis and heart failure over the long run. Considering that hormonal imbalance is known to occur in heart failure, ST2 and Gal‐3, which are involved in this process, may offer useful insight as they also increase in these circumstances as demonstrated by Kropfl et al ( 2023 ). We expected low values of these biomarkers in athletes since high plasma levels of Gal‐3 and ST2 are thought to be risk predictors in the general population and for patients with heart failure (Bayes‐Genis et al., 2013 ).…”

“…In an article in this issue of Experimental Physiology, Kröpfl et al ( 2023 ) has shown that Galectin‐3 (Gal‐3) and Suppression of Tumorigenicity‐2 (ST2) levels increase after acute exercise of different types (cycling and running) (Kröpfl et al., 2023 ). In this viewpoint, I will share our experience about those biomarkers in sport.…”