The Acute Phase Protein Complement 1 Inhibitor is an Indicator of Arterial Stiffness

An acute phase protein has been defined as a protein whose plasma concentration increases (positive acute phase protein) or decreases (negative acute phase protein) by at least 25 percent during an inflammatory condition (Gabay & Kushner, 1999). The complement system is a biochemical cascade and major effecter mechanism of humoral or innate immunity. However, the complement system also has the potential to damage host tissues; thus, its activation must be tightly regulated (Zanker, 2008). Spontaneous complement activation continuously occurs at a low level, and if such activation is not appropriately controlled, damage to normal cells and tissues can occur. Complement 1 (C1) inhibitor is a naturally occurring serine proteinase inhibitor that inhibits activated C1s and C1r, components of the classical complement pathway. It also inhibits other plasma serine proteinases, such as factors XIa and XIIa, plasmin, and kallikrein (Caliezi et al., 2000). C1 inhibitor is essentially an acute phase protein whose plasma level may increase 2to 2.5-fold during an inflammatory episode (Kalter et al., 1985; Woo et al., 1985). Arteriosclerosis or arterial stiffness is hardening of the artery due to the loss of elasticity through any cause. On the other hand, atherosclerosis is a chronic inflammatory disease of the artery characterized by hardening of the artery specifically due to an atheromatous plaque or inflammation in the arterial wall (Kostner et al., 2006; Jani & Rajkumar, 2006; Ridker & Silvertown, 2008; Wykretowicz et al., 2009). Atherosclerosis is the most common form of arteriosclerosis, and is known to be positively correlated with brachial–ankle pulse wave velocity (baPWV), a parameter of arterial stiffness (Imanishi et al., 2004; Jani & Rajkumar, 2006; Nicoletti et al., 2000; van Popele et al., 2001; Wykretowicz et al., 2009; Yamashina et al., 2003). baPWV is a non-invasive test for arterial stiffness that has been used in large-scale population studies, and has become available in the clinical setting (Yamashina et al., 2002). Previous studies have shown that activation of the complement system is involved in the pathogenesis of atherosclerosis (Bhatia et al., 2007; Fosbrink et al., 2006; Niculescu & Rus, 2004; Oksjoki et al., 2003, 2007; Thorbjornsdottir et al., 2005; Yasojima et al., 2001). If atherosclerosis develops, inflammation of the arterial wall, increased arterial stiffness, and accompanying activation of the complement system simultaneously occur and progress. Production of the acute phase protein C1 inhibitor may also increase to regulate over-activation of the complement system. This chapter describes the role of the