Endothelial cell apoptosis: a new focal adhesion assembly makes the difference.

E ndothelial cells (ECs) covering the inner surface of blood and lymphatic vessels 1 create an interface between circulating blood and lymph and the surrounding tissue. Hence, ECs are crucially involved in maintaining the integrity of all tissues. In addition, the formation of new vessel, eg, during wound healing processes, is determined by ECs. 2 Thus, the maintenance of a structural and functional inner vascular EC surface is of particular importance. However, during pathological conditions ECs may be induced to undergo apoptosis, a major hallmark of the progression of atherosclerosis and other conditions. As these pathologies are the major cause of death in the Western hemisphere, 3 it is of outstanding importance to understand the fundamental mechanisms of EC apoptosis. Improved knowledge about the underlying mechanisms and signaling pathways enables physicians and scientists to combat these maladaptive mechanisms and help care for patients suffering from these diseases. To date, the understanding of EC apoptosis still remains elusive and fragmentary. It is an established dogma that a variety of intracellular signaling cascades, such as those involving Fas/ Fas ligand, Bax/Bad, or caspases, are responsible for EC apop-tosis. 4 For example, the protein kinase B/Akt is a major effector of apoptotic inhibition by activating antiapoptotic signaling pathways of the Bcl-2 family. 4 Akt, in turn, is activated and stabilized by a variety of cellular signaling pathways. In recent years, focal adhesions (FAs) have been found to play important roles in Akt activation by their interaction with phosphatidylinositol-3-kinase, a major upstream effector of Akt. FA kinase is one important component in this interaction because it regulates cell survival via phosphatidylinositol-3-kinase/Akt signaling. 5 Besides FA kinase and other FA assemblies, a complex consisting of integrin-linked kinase (Ilk), pinch1/2, and α-parvin/β-parvin (IPP) is significant for tissue development. 6 Ilk represents the central component of this ternary complex, regulating the levels of pinch1/2 and α-parvin/β-parvin. Dependent on its molecular constitution, the IPP complex exerts divergent signaling pathways. Although being involved in a variety of signaling events, the IPP plays a prominent role in Akt signaling. 6 In this regard, the IPP complex also mediates EC survival by inhibiting apoptotic routes 7 (Figure, A). Although much is known about the intracellular signal-ing involved in apoptosis, the entire picture of the mediators controlling these processes is likely more complex. Because the extracellular matrix (ECM) surrounding ECs represents a sophisticated regulator of EC behavior, 8 it is reasonable to …