ABSTRACT

The endothelium is a specialized type of a thin mono-cellular layer and forms an interface between circulating blood in the lumen and the rest of immune cells. The primary role of endothelial cells is to maintain the tissue perfusion by providing necessary vascular tone, vascular permeability and thromboresistance (Drexler 1997, Esper et al. 2006). Vascular endothelial cadherin complex is the central component of endothelial adherens junctions which plays an important role in endothelial processes such as leukocyte extravasation and angiogenesis. Vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha and thrombin induce the transformation of stable junctions into focal adherens junctions (Huveneers et al. 2012). Focal adhesions are also important regulators of cell signaling, cell locomotion and cell adhesion. The normal function of the endothelium is highly dependent on the endothelial cytoskeleton. Disruption and dysfunction of the cytoskeleton may result in impairment of endothelial integrity (Lee and Gotlieb 2003). While the barrier function of the endothelium is regulated by small guanosine triphosphatases (small GTPases) and kinases by activation of the phosphoinositide 3-kinase (PI3K)/

Gazi University, Faculty of Pharmacy, Department of Toxicology, 06330, Hipodrom, Ankara, Turkey. E-mail: abengin@gmail.com

Akt pathway, microtubule function is arranged by the acetylation of tubulin (Hirase and Node 2012). PI3K/Akt serves as mediator in endothelial cell membrane depolarization which is followed by nicotinamide-adenine dinucleotide phosphate (NADPH)-oxidase mediated reactive oxygen species (ROS) generation (Chatterjee et al. 2012). Actually altered endothelial cell response due to oxidative stress leads to the impairment of endotheliumdependent vasodilatation which is called endothelial dysfunction. This state is associated with the development of infl ammation and vascular diseases (Esper et al. 2006, Dai and Dai 2010). Thus the earliest detectable changes in vascular diseases are observed in endothelial cells (Harrison 1997a).