**1. Introduction**

Vascular endothelium has a critical role in maintaining vascular tone, and changes in vascular flow are in complex interactions with endothelium. The importance of this particular function of the endothelium manifests in the fact that the term "endothelial function" is usually used to

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

describe the ability of endothelium to release vasoactive substances and thereby regulate blood flow. The basic principle of vascular function is that healthy blood vessels dilate normally and the diseased blood vessels exhibit a dysfunctional vasodilation. Therefore, all methods for endothelial function assessment are based on the ability of endothelium to respond (vasodilation or vasoconstriction) to a specific stimulus (vascular occlusion, pharmacological vasodilators, heating, etc.).

studies indicate that endothelium-derived hyperpolarizing factor (EDHF) plays a major role in vasodilation in skin microcirculation [9], whereas the results are still conflicting concerning the implication of prostaglandins [10–12]. A study on coronary endothelial function in young smokers reported that they had epicardial coronary endothelial dysfunction but preserved

The Markers of Endothelial Activation http://dx.doi.org/10.5772/intechopen.74671 393

The importance of maternal vascular adaptation to pregnancy is to increase blood flow and to assure the proper development of the fetus. Several possible biochemical biomarkers have been proposed to evaluate vascular/endothelial function in pregnancy. First among them is NO, one of most important endothelial vasodilators, which is produced by NO synthase (NOS). It is well accepted that NOS-3 expression levels are increased in uterine artery endothelium in pregnancy [14]. Prostacyclin (PGI2) also plays an important role in vasodilator response, and its concentration is elevated in pregnancy [15]. In order to estimate the real impact of prostacyclin on vascular tone, determination of thromboxane a2 (TXA2)/PGI2 ratio is needed. Since both TXA2 and PGI2 have very short half-life, only indirect measures can be made of stable metabolites in the blood (thromboxane b2 (TXB2) and 6-keto-prostaglandin F2a (6-ketoPGF2A)), and there is no technique which allows their monitoring in real time. It has been demonstrated that cyclooxygenase 1 (COX1) is upregulated in endothelial cells during pregnancy, and therefore induces a PGI2 increment [14]. EDHF is the third major player in endothelial vasodilation in pregnancy, causing smooth muscle relaxation. As it is not a single factor and there is still ongoing research to identify its specific components, it is described as spectrum of responses that are neither NO nor PGI2 mediated. Another limiting problem is that there is no appropriate method for its tracking. Although EDHF may seem as unnecessary pathway beside NO and PGI2, a number of studies showed an important role of EDHF in endothelium vasodilation in pregnancy, sug-

gesting that without EDHF, there would not be sufficient blood flow to the fetus [16].

Endogenous eNOS inhibitor ADMA concentrations were found to be significantly lower in pregnant women. However, this did not explain the improved flow-mediated dilation (FMD) in the correlation analysis [17, 18]. Also, endothelial function in normal pregnancy was not attenuated despite the significant increase in hsCRP, and pregnancy-related changes in the concentrations of proinflammatory cytokines, e.g., tumor necrosis factor alpha (TNF-α) and

It has been reported that the regulation of the NO-dependent pathway presents a key mechanism mediating endothelial adaptations to shear stress, including increased NO synthesis, increased expression and activity of antioxidative enzymes (e.g., superoxide dismutase (SOD) and catalase), and decreased oxidative stress level (reactive oxygen species (ROS) production) which all increases NO bioavailability. However, recent studies demonstrated that COX-dependent pathway and increased PGI2 synthesis take part in endothelial adaptations to shear stress, as well. Furthermore, a growing body of evidence suggest that increased shear stress generated by increased blood flow during exercise, presents a prime signal for

microvascular endothelial function [13].

interleukin 6 (IL-6), were nonsignificant [19].

**2.2. Biomarkers in exercise**

**2.1. Biomarkers in pregnancy**

Biomarkers are biological indicators of processes that are part of etiology of the diseases, and can, but do not have to be causal to diseases. One very important question is how specific and sensitive the marker is, since one molecule can appear in many conditions. Biomarkers of endothelial cell activation can be very diverse: biochemical/metabolic (such as plasma glucose, lipids, cytokines, asymmetric dimethylarginine (ADMA), high sensitive C-reactive protein (hsCRP), myeloperoxidase (MPO), cell adhesion molecules (CAMs), markers of coagulability, markers of oxidative stress, chemokines, microparticles, endothelial progenitor cells), functional biomarkers (such as flow-mediated dilation and other types of flowmetry, arteriographic measurements of vascular function) and structure (e.g., CIMT—carotid intimamedia thickness, angiogenesis, or rarefaction).
