**1. Introduction**

Endothelial cells (ECs) line the interior surface of blood cells and lymphatic vessels forming an interface between circulating blood or lymph in the lumen and the vessel wall. ECs are a thin layer of squamous cells. The vascular EC line the entire circulatory system from the large vessels

© 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.

to the smallest capillaries, thereby accommodating various levels of blood flow from the turbulent high pressures from large vessels entering and leaving the heart as well as small vessels such as that of the minute capillaries of the lungs, liver, kidneys, and the moderate vessels throughout the body. ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the EC of large vessels from microvascular ECs [1].

and coagulation factors in the intrinsic coagulation pathway generating more thrombin and formation of a fibrin mesh. The adhesion of platelets is facilitated by von Willebrand factor (vWF). vWF is a product of normal EC and is not synthesized after endothelial injury. The clotting pathway is also induced by cytokines such as tumor necrosis factor alpha (TNF-α) or interleukin 1 (IL-1) or bacterial endotoxin such as lipopolysaccharide (LPS) to secrete TF which activates the extrinsic clotting pathway [3]. In a tightly regulated system, the proteases and molecules of the coagulation cascade can be inhibited by circulating protease inhibitors, such as antithrombin, heparin cofactor II, TF pathway inhibitor and C1 inhibitor. These bind with the active sites of proteases, thereby inactivating them. In addition, coagulation factors can be degraded through activation of the protein C and protein S complex, synthesized by ECs as a cofactor that is then catalyzed by the presence of thrombomodulin and endothelial protein C receptor (EPCR). Other pathways of coagulation factor degradation are disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). ADAMTS13 cleaves the multimeric strands of vWF, thereby disrupting platelet adhesion. ECs synthesize tissue plasminogen activator (t-PA), promoting fibrinolytic activity to clear fibrin deposits from endothelial surfaces [3, 6]. Thrombin also binds to its protease activated receptor-1 (PAR-1) and induces a signaling cascade resulting in EC junctional gaps that lead to increased endothelial permeability [7].

Lung ECs also regulate the synthesis and metabolism of vasoactive compounds such as nitric oxide (NO) and endothelin-1 (ET-1), potent regulators of pulmonary vascular tone [8]. EC-derived NO, synthesized by the endothelial nitric oxide synthase (eNOS) from the precursor L-arginine, regulates the healthy endothelium. Antithrombotic effects of EC-derived NO

The enzyme eNOS depends on intracellular calcium (Ca2+) level. In response to a rise in EC intracellular Ca2+ eNOS catalyzes the production of NO. The Ca2+-dependent eNOS synthesizes small amounts of NO until the Ca2+ levels decrease. This Ca2+-dependent eNOS provides the basal release of NO and is sufficient to inhibit the adhesion and activation of platelets

Cytokines are small soluble proteins that are important in cell signaling and can change the behavior or properties of cells. Cytokines can be secreted by many cells including pulmonary ECs [11]. Cytokines can be grouped into families including the interferons, the chemoattractants (chemokines), the tumor necrosis factors (TNFs), the interleukins (IL-2, IL-3, IL-4 etc.), the epidermal growth factor family (EGF) and transforming growth factors-alpha and beta (TGF-α and β), the growth factors include vascular endothelial growth factor (VEGF and others) that are important in vasculogenesis and angiogenesis. The VEGF family of growth fac-

Pulmonary EC express adhesion molecules and pro and anti-inflammatory cytokines and are intricately involved in inflammatory processes [12, 13]. It was shown that there is a central role via the sphingosine-1-phosphate (S1P) receptor in pulmonary endothelium for regulating an excessive pro-inflammatory cytokine and chemokine production in an influenza virusinduced cytokine storm [14]. A deficiency of alpha 1-antitrypsin (A1AT), a protein that has been shown to trigger an inflammatory response leading to increased circulating concentrations of

and inhibition of plasminogen activator inhibi-

Pulmonary Vascular Endothelial Cells http://dx.doi.org/10.5772/intechopen.76995 289

are likely related to release of prostaglandin I<sup>2</sup>

providing homeostasis in unstimulated ECs [10].

tors restores the oxygen supply to tissues in hypoxic conditions [12].

tor-1 (PAI-1), a prothrombotic protein [6, 9].
