# Dynamic Correlation between Platelet Aggregation and Inflammatory-like State in Athlete Horses
## 4 Discussion
Subsequently, muscle damage per se elicits a repair response, including macrophage entry into the muscle, causing further IL-6 production [36]. The exercise-activated muscle has been also suggested to modulate platelets' reactivity. According to the results obtained herein, decreased platelet aggregation values were found after exercise compared with the rest condition, whereas no significant changes in slope were observed. These results complied with the findings obtained in previous studies carried out on athletic horses [21; 30]. The blood hemoconcentration occurring during physical exercise leads to an increased concentration of sodium citrate, resulting in a lowered ionized calcium level and, consequently, decreased platelet aggregation [37]. Moreover, the catecholamine increase knownto occur during exercise could contribute to the decrease in platelet aggregation after physical activity [38; 39; 40]. As a matter of fact, increased adrenaline levels result in decreased platelet aggregation, probably due to adrenergic receptor downregulation [38]. Noradrenaline is capable of exciting endothelial cells to release two strong potent inhibitors of platelet aggregation (i.e., nitric oxide and prostacyclin) [39]. Effectively, the increased prostacyclin production and plasma nitric oxide metabolites may suppress platelet reactivity [40]. It is likely that the changes observed in platelet reactivity represent a protective endothelial mechanism of the organism through the production of nitric oxide in response to physical exercise. Noteworthy in this survey is that platelet aggregation and slope showed a strong negative correlation with the serum values of CRP and \(\alpha\)1-globulins after exercise, suggesting a link between inflammatory status and platelet responsiveness during exercise. These relationships immediately after exercise (within 5 min from the end of exercise) could be due to the high adaptation response of the body systems of horses, including the inflammatory and hemostatic systems, because of the recent stressful event (i.e., physical activity). As a matter of fact, the significant relationship among the investigated parameters was lost in the other conditions (at rest) and after 30 and 60 min from the end of the exercise, when the horse's homeostasis is recovering. It must be taken into account that the horses enrolled in the present study were regularly trained with a standard training program; thus, the biochemical adaptation to the stress induced by physical exercise may have been optimized by training. A possible inflammatory-thrombotic link has been proposed in a study on human blood ex vivo and in murine blood in vivo in which a monocyte-platelet aggregation promotion by CRP has been demonstrated [17]. An in vitro study investigating the role of CRP in thrombus formation on different vascular substrates under flow conditions suggested that the CRP has contrasting effects on thrombus formation according to its conformation. Whereas native CRP had no effect, the monomeric forms of CRP strengthened the activation and adhesion of platelet as well as thrombus growth under arterial flow conditions [41]. It has been demonstrated that circulating blood native CRP could be transformed into Orthrombotic monomeric CRP under flow conditions on the surface of platelets attached to collagen [42]. In addition to collagen, other substrates that trigger platelet adhesion and aggregation also support CRP dissociation [18]. It has been suggested that a vascular injury with mural platelet adhesion can induce a dissociation of native CRP into monomeric CRP, highlighting that this dissociation is dependent on deposited activated platelets [18]. Contrariwise, dated investigations showed that the effect of CRP on platelet aggregation is not consistent with enhanced thrombosis as, when applied to platelets, CRP suppresses aggregation [43; 44].