# Dynamic Correlation between Platelet Aggregation and Inflammatory-like State in Athlete Horses
## 1 Introduction  
A number of external and internal factors negatively disturb the homeostatic equilibrium of organisms, causing the so-called state of stress. Stressful events perturb an organism's welfare status and induce energy-consuming mechanisms to counter the onset of ill effects [1]. Several stress markers that indicate that an individual is not in physiological comfort are considered and investigated in order to study the stress response of organisms and their capability to restore homeostasis [2]. Indeed, events starting from the disturbance of homeostasis initiate a series of reaction cascades involving oxidative, inflammatory and proteomic reactions [3, 4, 5, 6]. These stress-induced reactions are well orchestrated and so interlinked that the generation of one compound influences the formation of another one. One example is represented by the generation of pro-inflammatory interleukins that influence the production of anti-inflammatory counterparts [4]. Among the several effects of the inflammatory reaction to stress conditions, the onset of an acute-phase response (APR) is well known. The APR is a rapid and non-specific response to any kind of injury [7] during which acute-phase proteins (APPs) are produced in the liver following the activation of receptors on various target cells by pro-inflammatory cytokines. The serum protein pattern generated by the serum electrophoresis analysis gives a good picture of the acute-phaseserum protein response. Serum proteins include four fractions, namely albumin and alpha (\(\alpha\))-, beta (\(\beta\))- and gamma (\(\gamma\))-globulin fractions [8]. The \(\alpha\)-globulin fraction includes the C-reactive protein (CRP) known as a positive APP since its concentration increases during an inflammatory response [7]. In horses, the CRP is a moderate APP and an increase in its concentration has been reported after castration, in enteritis, arthritis, laminitis and induced inflammation [9]. A reaction analogous to the APR in inflammatory conditions has also been reported after exercise in humans [10; 11] and in athletic horses [12; 13]. As a matter of fact, physical exercise induces various stress responses and metabolic adaptations. Depending on the duration, intensity and type of physical exercise, as well as on the training condition of the subject, equine metabolism has to adapt to nervous, cardiovascular, hemostatic, endocrine and respiratory system requirements. The exercise-induced APR has been characterized by changes in pro-inflammatory and anti-inflammatory cytokines, CRP and other acute-phase proteins, including albumin, fibrinogen and serum amyloid A [11; 12]. Similarly to APPs, the platelet parameters are markers reflecting the systemic inflammatory response besides the activity/severity of many diseases [14; 15]. Though many reports have been published on the effects of physical exercise on hemostasis and acute-phase proteins in horses, few studies have included in the same experimental protocol the simultaneous evaluation of CRP, albumin, globulin fractions and platelet aggregation. Specifically, data regarding the linkage between platelet activation indices and inflammatory markers are scarce and contradictory [16; 17; 18]. Moreover, in horses, the change in serum CRP together with electrophoretic protein pattern, including indirect markers of activation of inflammation and immunity, and their relationship with platelet activity have not been characterized in the context of exercise.  
On the basis of such considerations, the aims of this study were (i) to evaluate the dynamic change in serum CRP, total proteins, albumin, globulin fractions, the maximum degree of platelet aggregation and the initial velocity of aggregation in response to exercise in well-trained jumper horses; and (ii) to assess whether the serum concentrations of CRP, albumin and globulin fractions are correlated with the platelet activity indices in order to clarify if and how platelet aggregation is modulated by inflammation status in athletic horses following physical exercise.