Time course studies on the initiation of complement activation in acute myocardial infarction induced by coronary artery ligation in rats

Abstract

This study attempted to probe the role of complement activation in promoting acute myocardial infarction (AMI) induced by coronary artery ligation (CAL) in rats. The surgical technique used in this study significantly reduced early mortality (95% survival rate) and also reduced the variation in infarct size (33+/-1.87%) at 32 h after surgery. Time course studies on the initiation of AMI at various time points were carried out using physiological, biochemical, histopathological and electron microscopical techniques. Serum markers and activities of lysosomal hydrolases were found to be significantly elevated at the 8th hour post ligation. Histological studies showed polymorphonuclear cells emigration and total coagulation necrosis. Transmission electron micrograph exhibited mild distortion of muscle fibres and mitochondrial rupture with disrupted cristae. Immunoblotting studies confirmed the presence of alpha2-macroglobulin which supported the inflammatory response at 8th h of post ligation. The initiation of the complement (C) activation was observed by the increase in the level of the soluble form of the membrane attack complex (sC5b-9) in serum and left ventricle. Immunoexpression studies confirmed the initiation of the terminal C activation as shown by the expression of C5, C6, C7, C8, C9 and sC5b-9 complex at the 8th h of AMI. This study conclusively demonstrated that initiation of the C activation was observed to be significant at the 8th h of AMI induced by CAL in rats.

Bioactive Lipids and Cationic Antimicrobial Peptides as New Potential Regulators for Trafficking of Bone Marrow-Derived Stem Cells in Patients with Acute Myocardial Infarction

“…Erythrocytes can take up and release S1P, and this buffering function likely explains the * · 25 higher concentration of S1P in PB as compared with tissues. Innate immune system activation after ischemic myocardial injury, including the CC [44][45][46][47][48], may play an important role in the release of S1P from blood cells such as activated platelets [60][61][62], RBCs [58,63], and endothelial cells [28,64]. We demonstrate for the first time that plasma levels of S1P and C1P are significantly elevated after AMI (Fig.…”

“…Activation of CC and the resultant generation of C5b-C9 (membrane attack complex) may enhance release of S1P from RBCs. The CC was activated in AMI patients [44][45][46][47][48], and in our AMI population, C5b-C9 levels were elevated in serum (Supplementary Fig. S1; Supplementary Data are available online at www.liebertpub.com/scd).…”

“…2B, C). The higher plasma levels at BSL may also reflect the release of C1P from damaged cardiomyocytes as recently shown in the murine model of acute heart ischemia [48]. However, the role of C1P in non-HSC mobilization requires further studies, given the limited and transient increase in its levels and somehow the lack of temporal correlation with the number of mobilized nonHSCs.…”

“…Interestingly, many of the earlier mentioned mechanisms and cells are activated in the setting of AMI. The CC is activated locally at sites of myocardial infarction with elevated levels of C5b-9 both in the myocardium and plasma [48]. Recent evidence suggests the role of C5b-9 and other members of the CC in the mobilization and homing of BM stem cells [28,38,39].…”

Pluripotent Stem Cell-Engineered Cell Sheets Reassembled with Defined Cardiovascular Populations Ameliorate Reduction in Infarct Heart Function Through Cardiomyocyte-Mediated Neovascularization

“…In this study, we performed the sheet transplantation at 1 week after MI induction (subacute stage). This should be the optimal transplantation timing, avoiding damage of transplanted cell with acute inflammation and obtaining sufficient tissue repair before fibrotic scar formation in chronic stage [55,56]. However, sufficient long-term engraftment was not achieved in this study.…”