The complement system in ischemic heart disease.

Abstract

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p<0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p<90.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r=0.71) and inversely related to the ejection fraction (r= -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated. (Circulation 1990;81:156-163) R ecent studies in experimental models suggest that acute myocardial ischemia is associated with activation of the complement system. First, studies in the baboon have established that C3, C4, and C5 are deposited in most infarction myocardial fibers.12 Second, by inactivating the complement system in vivo with cobra venom factor, a significant reduction in myocardial damage was achieved in an animal model.3 Also, a few studies report the complement activation in vivo in patients with acute myocardial infarction (AMI).4-6 However, it is not clear whether the activated complement system affects the myocardial necrotic size and cardiac function in human myocardial infarction. It is also unknown whether or not the complement system is activated in patients with angina pectoris (AP). This study assessed complement activation in patients with AMI and AP by directly measuring by-products of the reaction. The degree of activation of the complement system was compared with the hemodynamic manifestations and peak creatine phosphokinase (CPK) in patients with AMI. MethodsThe study group consisted of 31 patients with AMI, 17 patients with unstable angina pectoris (UAP), 19 patients with stable angina pectoris (SAP), and 20 normal volunteers (Table 1). AMI was defined by at least two of the following: 1) angina lasting longer than 30 minutes, unrelieved by rest, 2) serum creatine kinase-MB fraction greater than 5%, 3) inversion or elev...

CR1 genotype and haplotype involvement in coronary artery disease: The pivotal role of hypertension and dyslipidemia

“…In light of immunohistochemical and immunoelectron microscopic data, the cell type most susceptible to attack by complement is smooth muscle cell. In particular, the complement cascade, once activated during myocardial ischemia, appears to mediate immune and inflammatory responses in ischemic myocardium (40). Complement activation contributes to myocardial damage through various pathways, including activation of leucocytes and endothelial cells, increase in apoptosis, up-regulation of genes involved in cytokine production and interruption of nitric oxide synthase activity (41).…”

Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator.

“…A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The AMI,5,6 although two other studies (one, however, was limited to the early phase of AMI) did not report complement activation. 78 We have recently been unable to detect signs of complement activation in plasma during the acute phase of uncomplicated myocardial infarction.…”

Complement activity and pharmacological inhibition in cardiovascular disease

“…Although immunochemistry studies have shown evidence of complement activation in these plaques (17), only a few studies have looked at the blood levels of complement proteins. Yasuda et al (18) described elevated sC5b-9 levels that correlated with infarct size in patients with cell necrosis but only a modest elevation of C3a, and not of sC5b-9, in those with unstable angina and no cell necrosis. The findings suggest strong complement activation in the former condition, and self-limited activation not progressing to activation of the terminal pathway in the latter (18).…”

“…Yasuda et al (18) described elevated sC5b-9 levels that correlated with infarct size in patients with cell necrosis but only a modest elevation of C3a, and not of sC5b-9, in those with unstable angina and no cell necrosis. The findings suggest strong complement activation in the former condition, and self-limited activation not progressing to activation of the terminal pathway in the latter (18). Another study reported an elevation of sC5b-9 levels in 47 patients with unstable angina and elevated CRP levels without, however, assessing the proximal components of the cascade (19).…”