**Profilin, and Vascular Diseases**

Mohammad T. Elnakish and Hamdy H. Hassanain

*Department of Anesthesiology, Dorothy M. Davis Heart & Lung Research Institute Molecular, Cellular, and Developmental Biology Program The Ohio State University, Columbus, OH USA* 

### **1. Introduction**

64 Biochemistry

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Actin is a highly dynamic network. It is essential for several important activities, such as muscle contraction and transmembrane signaling (Luna & Hitt, 1992; Salmon, 1989). Actin consists of actin filaments and a variety of associated proteins (Schmidt & Hall, 1998). Many proteins associated with the actin cytoskeleton control actin assembly and disassembly. These proteins regulate actin assembly at multiple levels, including the organization of actin monomers into actin polymers (Schmidt & Hall, 1998).

One key actin-regulatory protein is profilin, which associates with polymerization of actin. Profilin is a ubiquitous small (12–15 kDa) actin-binding protein expressed in eukaryotes (Kwiatkowski & Bruns, 1988; Magdolen et al., 1988; Sonobe et al., 1986; Tseng et al., 1984; Valenta et al., 1991a, b; Widada et al., 1989) and some viruses (Machesky et al., 1994). Profilin plays an important role in the regulation of actin polymerization in a number of motility functions (Haarer & Brown, 1990). The ability of profilin to bind to many ligands suggests that profilin is involved in signal transduction and may link transmembrane signaling to the control of the microfilament system (Korenbaum et al., 1998; Pantaloni & Carlier, 1993).

Early biochemical studies indicated that profilin interacts with actin in a 1:1 ratio and participates in the addition of monomers at the free barbed end of the filament then disassociates at the barbed end (Pantaloni & Carlier, 1993). Latest work has suggested several more functions of profilin aside from its monomer-sequestering ability. Profilin promotes the exchange of adenine nucleotide bound to actin monomer and also effectively lowers the critical concentration of monomer actin for polymerization of actin (Borisy & Svitkina, 2000; Theriot & Mitchison, 1993). It also promotes nucleotide exchange on an actin monomer by lowering the affinity of the actin monomer for its bound nucleotide by 1000 fold (Goldschmidt-Clermont et al., 1991).

It became progressively clear that profilins are vital constituents of the cytoskeleton. Additionally, the role of profilins in several cytoskeleton-based processes of clinical relevance has been proven. Several studies showed abnormal profilin levels in some pathological conditions. For example, high levels of profilin expression have been reported in human gastric cancer (Tanaka et al., 1992). On the contrary, profilin-I has been described as a tumor suppressor in some other types of cancer such as breast cancer (Das et al., 2009; Zuo et al., 2007). Another clinical problem in which profilins may be involved is the lateral spreading of some infectious diseases (Pistor et al., 1995; Smith et al., 1996; Zeile et al., 1996). Moreover, profilins got a clinical consideration in other unexpected milieu. In this regard, profilins have been reported as major allergens implicated in pollen and food allergies in approximately 20% of type I allergy patients (Ebner et al., 1995; Valenta et al., 1991c, 1992). Furthermore, we (Hassona et al., 2010, 2011; Moustafa-Bayoumi et al., 2007) and others (Caglayan et al., 2010; Romeo & Kazlauskas, 2008; Romeo et al., 2004, 2007) have shown that profilin-I is an unexpectedly novel molecule that plays a highly significant role in vascular problems that predict a higher risk for developing arteriosclerosis, hypertension, stroke, heart failure, and finally death. Therefore, the aim of this chapter is to shed light on the significance of profilin-I via understanding the molecular and cellular aspects of this molecule, and its role in the vascular diseases.
