We observed a significant difference between the baseline EN levels and the levels after 8 months (+33,5%) in a group of subjects with proven performance gain. Furthermore, the increasing tendency of the increase (measurement every 2 months) was significant. The beneficial effects of exercise on traditional cardiovascular risk factors such as hypertension, diabetes mellitus or dyslipidemia do not fully account for the magnitude of cardiovascular risk reduction. Effects of physical exercise on the vasculature, in particular the vascular endothelium, provide a plausible contribution to the exercise-related risk reduction in cardiac events [
7]. The healthy vascular endothelium, as a paracrine and endocrine organ, ensures vascular homeostasis. Any kind of noxa tipping the balance of this sensitive system leads to endothelial dysfunction. Endothelial dysfunction is a well established response to the classic cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidemia, overweight/adipositas, physical inactivity and smoking and precedes the development of atherosclerosis. It is a basic pathomechanism in cardiovascular disease (CVD) and mainly characterized by increased inflammation, proliferation and coagulation [
8]. Several laboratory parameters serve as surrogate for the performance of body systems such as C-reactive protein (CRP) for the inflammation status or high-density and low-density lipoprotein for the lipid profile and play a central role in the pathogenesis, diagnosis but also prevention of CVD.. The preventive effect of physical activity might be caused by several mechanisms affecting inflammation [
9], angiogenesis [
10] and calcification [
11]. Recently published studies suggest an involvement of EN in inflammation, cancer progression an angiogenesis: EN is overexpressed in septic patients, patients with gliomas [
12], non-small cell lung cancer tumours [
13] and other types of cancer [
14] and furthermore was suggested a predictive marker of all-cause mortality and cardiovascular events in patients suffering chronic kidney disease [
15]. Several study suggested increased EN levels as common predictor of the endothelium-dependent inflammatory processes. The overexpression of EN might affect two factors which are involved in acute inflammatory response, reperfusion and ischemia injury and antitumor response: LFA-1 (lymphocyte function-associated antigen-1) and ICAM-1 (intercellular adhesion molecule-1). EN may be involved in the regulation of the LFA-1/ICAM-1 pathway, resulting in decreased leukocyte activation by LFA-1, which may affect the lymphocyte homing to sites of inflammation and aggregation. Consequently, leukocyte adhesion and activation may be affected [
14]. EN was also shown to correlate with the intima media thickness (an early sign of atherosclerosis) and BMI in patients suffering systemic lupus erythematosus [
16]. These findings consolidated the position of EN as atherosclerosis surrogate. Interestingly, it was also shown that high levels of EN expression correlate with angiogenic factors, such as VEGF-A (vascular endothelial growth factor A) and FGF-2 (fibroblast growth factor-2) and might therefore have an influence on angiogenesis, however, the exact mechanism is not known yet [
13]. A recently published study by Cimen et al. [
17] showed that patients with ischemic heart disease and patients with microvascular angina have significantly higher plasma EN levels compared to controls. They furthermore found an independent positive correlation between EN levels and the SYNTAX score.
Taken together the results of the mentioned studies, EN is somehow “tainted with a bad repute”. However, as mentioned above, EN also shows a potential anti-inflammatory activity through inhibition of the LFA-1–dependent leukocyte function [
3] and might collude with VEGF leading to increased angiogenesis. Since physical activity is well known to counteract/retard atherosclerotic processes, improve angiogenesis and vascularization and acts preventive against several types of cancer, our results would be contradictory to the current knowledge. Our results show a physical activity induced increase in serum EN levels by about 33,5%. The EN increase might represent exercise-derived activation of the vascular endothelium. We believe that EN plays also an important role in physiological processes and that a certain amount of circulation EN is absolutely necessary e.g., for adequate angiogenesis, anti-inflammation and probably wound healing. Microarray analysis has revealed that during angiogenesis tip cells specifically express endocan in much high level in comparison to rest of the vasculature [
18].
EN should rather be considered as a mediator which is involved in several physiological and pathological processes and whose expression can be significantly influenced by long term physical activity.
However, within our study population, we could not state an influence of physical activity on circulating OPG amounts although the study population was quite large, the follow up close-meshed and the observation period long. As vascular calcification is a process with slow progression it is conceivable that the observation period was too short to state an impact of sports on OPG levels.