Complement System Activation in Cardiac and Skeletal Muscle Pathology: Friend or Foe?

Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Athens, 11527, Greece.
Advances in Experimental Medicine and Biology (Impact Factor: 1.96). 02/2013; 734(VIII):207-18. DOI: 10.1007/978-1-4614-4118-2_14


A major goal in current cardiology practice is to determine optimal strategies for minimizing myocardial necrosis and optimizing cardiac repair following an acute myocardial infarction. Temporally regulated activation and suppression of innate immunity may be critical for achieving this goal. Extensive experimental data in various animal models have indicated that inhibiting complement activation offers protection to cardiac tissue after ischemia/reperfusion. However, the results of clinical studies using complement inhibitors (mainly at the C5 level) in patients with acute myocardial infarction have largely been disappointing.
In cases in which complement activation participates in the initial events of muscle cell destruction, as in autoimmune myocarditis or autoimmune muscle disorders, inhibition of complement activation is expected to prove a successful treatment. In other pathologic conditions in which complement is recruited by degenerating or dying muscle cells, as in ischemia, the ideal approach is probably to modulate rather than abruptly blunt complement activation. Beneficial effects of complement action with regard to waste disposal, recruitment of stem cells, regeneration, angiogenesis, and better utilization of energy sources under hypoxic conditions may also prove important for successful disease treatment. Patient outcome after myocardial infarction almost certainly depend upon the combined activation of several distinct but potentially interrelated signaling pathways, suggesting that a combination of treatments targeted to different pathways should be the therapy of choice, and modulation of complement could be one of them.

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    ABSTRACT: Myocardial infarction (MI) is a serious heart disease. The cardiac cells of patients with MI will die due to lack of blood for a long time. In this study, we aimed to find new targets for MI diagnosis and therapy. We downloaded GSE22229 including 12 blood samples from healthy persons and GSE29111 from Gene Expression Omnibus including 36 blood samples from MI patients. Then we identified differentially expressed genes (DEGs) in patients with MI compared to normal controls with p value < 0.05 and |logFC| > 1. Furthermore, interaction network and sub-network of these of these DEGs were constructed by NetBox. Linker genes were screened in the Global Network database. The degree of linker genes were calculated by igraph package in R language. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis were performed for DEGs and network modules. A total of 246 DEGs were identified in MI, which were enriched in the immune response. In the interaction network, LCK, CD247, CD3D, FYN, HLA-DRA, IL2, CD8A CD3E, CD4, CD3G had high degree, among which CD3E, CD4, CD3G were DEGs while others were linker genes screened from Global Network database. Genes in the sub-network were also enriched in the immune response pathway. The genes with high degree may be biomarkers for MI diagnosis and therapy.
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