Kulkarni and Afshar-Kharghan died from AMI (Pinckard et al 1980; McManus et al 1983; Laine et al 2002). Patients with MI have increased post-infarction plasma levels of C5b-9 (Langlois and Gawryl 1988). Actually, levels of C3, C8, C9, and FB were all signiﬁcantly increased in patients 6 and 12 hours after admission for MI (Halas et al 2005). C5b-9 was also found to be present in higher quantities in pathologic specimens of atherosclerotic plaques from patients with acute coronary syndrome (ACS) as compared to those with stable angina (Meuwissen et al 2006). Interestingly, the presence of C5b-9 in necrotic tissue was associated with the loss of CD59 in postmortem studies on patients who died from MI (Väkevä et al 1992). Recently, several complement proteins have been studied as predictive markers in CAD leading to MI. For example, there was a substantial correlation between C3 levels and several cardiovascular risk factors, such as blood pressure, body mass index, and serum lipid levels (Engström et al 2007). C3 levels were shown to be a strong predictor of MI, especially in men, and C3a levels were elevated in patients with unstable angina as compared to those with stable angina (Muscari et al 1995; Kostner et al 2006). Finally, C3 and C4 levels in patients admitted for AMI were signiﬁcantly higher than in patients with stable angina or healthy controls, and the serum C3/C4 ratio could possibly be used as a marker of subsequent cardiovascular events after a previous manifestation of ACS (Iltumur et al 2005; Palikhe et al 2007). Additionally, elevated C5a levels were shown to be associated with an increased risk of MI, PCIs, coronary artery bypass graft (CABG) surgery, carotid revascularization, stroke, or death in patients with advanced atherosclerosis (Speidl et al 2005). C-reactive protein (CRP) interacts with the complement system. It was shown that CRP binds to damaged cardiomyocytes and activates the complement system (Kaplan and Volanakis 1974; Siegel et al 1974; Volanakis and Kaplan 1974; Volanakis 1982; Jiang et al 1992). The level of deposited CRP correlated with the extent of activation of the complement system in infarcted myocardial tissue as determined by measuring levels of complement proteins, CRP, and CRP-complement protein complexes (Nijmeijer et al 2003). In a rat model of MI, injection of human CRP increased the size of infarcted myocardial tissue. This effect of CRP was blocked by CVF-induced complement depletion even two hours after induction of MI (Griselli et al 1999). The mainstay of treatment for MI is early revascularization through thrombolytic therapy, percutaneous coronary inter- vention (PCI), or CABG surgery. However, revascularization 678 carries with it the risk of ischemia-reperfusion injury, in which the complement system is activated. Reperfusion has been known to cause arrhythmias, microvascular dysfunction, and even cell death (Verma et al 2002). Reperfusion can also cause a condition known as myocardial stunning, which refers to diminished contractility of ischemic but still viable myocardium after full revascularization (Braunwald and Kloner 1982). The complement system has been shown to be involved in the acute inﬂammatory response associated with ischemia-reperfusion injury (Yasuda et al 1990; Eltzschig and Collard 2004). Activation of the complement system increases vascular permeability, activates endothelial and inﬂammatory cells, coagulates blood, and causes cell lysis. Therapy Several anticomplement therapies have been tried in different animal models of MI and ischemia-reperfusion, as well as in human clinical trials. One of the ﬁrst anticomplement reagents used was the soluble form of complement receptor 1 (sCR1), a recombinant protein that comprises the extracellular part of the complement regulatory protein CR1. In an isolated rat model of ischemia-reperfusion injury, sCR1 was able to prevent post-ischemic myocardial contractile dysfunction and enhance coronary blood ﬂow (Shandelya et al 1993). sCR1 modiﬁed with the addition of a myristoylated peptide sequence, creating a molecule known as Mirococept and giving sCR1 the ability to bind to cell membranes, decreased infarct size, reduced serum troponin I, and resulted in a lower amount of complement deposition and myocardial apoptosis in a pig model of AMI (Banz et al 2007). C1-INH has also been used with some success in different models of MI and ischemia-reperfusion. In a cat model of ischemia-reperfusion, C1-INH given just before reperfusion reduced infarct size by 65% (Buerke et al 1995). In a rat model of MI, C1-INH suppressed C3 mRNA expression and protein synthesis, while in cultured rat cardiomyocytes, C1-INH blocked deposition of C3 (Fu et al 2006b). In the same model of MI in rats, C1-INH protected against cardiomyocyte apoptosis, improved cardiac function, reduced infarct size, and decreased inﬁltration by neutrophils (Fu et al 2006a). Treatment with C1-INH has also been studied in patients with MI. In one study, 22 patients received a loading dose of C1-INH followed by a continuous 48-hour infusion at least 6 hours after the onset of symptoms (de Zwaan et al 2002). In this small study, a C1-INH dose-dependent reduc- tion in activation fragments of C4 was shown. In 13 of the 16 patients who received thrombolytic therapy and C1-INH, Biologics:Targets & Therapy 2008:2(4)