Endothelial integrins and their role in maintaining the integrity of the vessel wall

Abstract

Integrin receptors The subendothelial matrix is, in general, thrombogenic surface that promotes platelet adhesion and the activation of the coagulation system. In normal conditions the presence of the endothelium represents good protection against thrombotic phenomena and plasma protein infiltration in the vascular media. The capacity of endothelial cells to remain attached to the vascular surface and to migrate and proliferate to cover exposed subendothelial structures is an important defense mechanism against the development of vascular injury. Endothelial cell interaction with matrix proteins is also of importance in neovascularization. The components of the extracellular matrix can promote cell proliferation and motility and provide an anatomical guide for the formation of new vessels [1]. The extracellular matrix therefore exerts more complex role than just providing substrate for cell attachment. Matrix proteins bind to specific receptors on the cell surface and this interaction can transfer intracellular signals. Many of endothelial receptors for matrix proteins, characterized so far, belong to the family of integrins. The integrin family consists of series of heterodimers involved in variety of cell adhesion functions [2—9]. Almost all cell types express these structures and integrins extend through most of the phylogenetic tree. These receptors have several structural and functional homologies so that it is believed that they differentiated from common ancestral gene. All integrins are formed by two non-covalently linked subunits: the larger termed chain and the smaller /3 chain. A subclassification of the integrin family has been attempted based on the observation that some members have the same f3 chain but different chains [2]. This resulted in the original definition of three subfamilies: the f3 or VLA (very late antigens) [61, the /32 or leu-cam (leukocyte adhesion molecules) [10], and the /33 or cytoadhesins [11]. However, three additional /3 chains have been recently sequenced: /3. [12—15], f3 [16] also called [17, 18] or f3, [19], and /36 [20]. At least three additional /3 chains have been described: /3,, in lymphocytes [21], the /3 chain of the melanoma laminin receptor [22], and /33b in macrophages [23]. In addition, it was found that some subunits have the capability to link to more than one /3 subunit. For instance, a can bind to /33, /3 [24-26], 136' (3 [17], and /33b [23]; a4 can bind to /3 [6] and /3,, [21], and a6 to [27] and 134 [12—15], thus making the original subfamily definition insufficient. Some integrins, but not all of them, recognize sequence of only three amino acids (arginine, glycine and aspartic acid, RGD) in the ligand [31. Many proteins containing this sequence, but not all of them, are recognized by an integrin receptor. The list includes large number of extracellular matrix and plasma proteins such as fibrinogen, vitronectin, fibronectin, thrombospondin, von Willebrand factor, bone sialoprotein [28] but also non-adhesive proteins such as thrombin [29]. Despite the similarities in the cell binding sequence in ligand proteins, the cell can recognize them individually through specific and separate receptors.