Loss of plasma membrane integrity, complement response and formation of reactive oxygen species during early myocardial ischemia/reperfusion

Abstract

Loss of plasma membrane integrity (LPMI) is a hallmark of necrotic cell death. The involvement of complement and ROS in the development of LPMI during the early stages of murine myocardial ischemia-reperfusion injury was investigated. LPMI developed within 1 hour of reperfusion to a level that was sustained through 24 hours. C3 deposition became significant at 3 hours’ reperfusion and thus contributed little to LPMI prior to this time. SOD1 transgenic mice had significantly less LPMI compared with WT mice at 1 hour of reperfusion but not at later time points. Catalase transgenic mice were not protected from LPMI at 1 hour’s reperfusion compared with WT mice, but had 69% less LPMI at 3 hours’ reperfusion. This protection was transient. At 24 hours’ reperfusion the LPMI of catalase transgenic mice was identical to that of WT mice. The delayed benefits of over-expressed catalase compared with SOD1 are consistent with its antioxidant action downstream of SOD1. The onset of LPMI occurs within 1 hour of reperfusion and is maintained through 24 hours. ROS contribute significantly to LPMI during the first 3 hours of reperfusion, while complement deposition, which becomes significant after 3 hours’ reperfusion, may contribute thereafter.

Inactivated pseudomonas�aeruginosa protects against myocardial ischemia reperfusion injury via Nrf2 and HO‑1

“…MDA and LDH, which are biological products of ROS and lipid peroxidation, indicate the degree of lipid peroxidation in the body and subsequently indirectly reflect the degree of myocardial injury (24). SOD and CAT are the main antioxidant enzymes responsible for the mobilization of free radicals (25). The present study revealed that IPA decreased LDH and MDA levels and increased SOD and CAT activities in myocardial tissues and serum samples, confirming the myocardial protection of IPA through the inhibition of lipid peroxidation and increased ROS removal.…”

Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

“…39 However, the significant downregulation of the humoral immune response concomitantly with both the alternative and classical complement pathway in our cohort would suggest that ischemia, in the absence of reperfusion, may not lead to an immediate increase in these pathways as previously described. This is supported by very low complement deposition ( C3d ) in brain-dead donor hearts that had ischemic injury without reperfusion, 40 by the lag in C3 deposition compared to the loss of plasma membrane integrity during early myocardial ischemia, 41 and by the initial decrease in serum C3 levels in pediatric cardiac surgical patients. 42 …”

Ischemia/Reperfusion

“…Subsequent studies demonstrated increased expression for all of the classical complement cascade proteins in ischemic tissues (804, 876). Postischemic complement activation is triggered by release of subcellular membrane consistuents secondary to cell necrosis (127, 248, 461, 672). Complement depletion or treatment with function-blocking antibodies that target specific proteins in the cascade have proven to be very effective in limiting postischemic inflammation and tissue injury, and constitute some of the strongest evidence supporting a role for complement cascade in I/R (76, 167, 251, 522, 530, 739, 795, 838, 845, 904).…”