Complement and its implications in cardiac ischemia/reperfusion: strategies to inhibit complement
| Autor: | Marc Fontaine, Tiphaine Monsinjon, Vincent Richard |
|---|---|
| Přispěvatelé: | Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2001 |
| Předmět: |
MESH: Complement Activation
Myocardial Ischemia Ischemia Myocardial Reperfusion Injury Inflammation MESH: Myocardial Ischemia/physiopathology 03 medical and health sciences 0302 clinical medicine MESH: Complement Inactivator Proteins/therapeutic use MESH: Complement System Proteins/physiology medicine Humans Pharmacology (medical) Anaphylatoxin Complement Activation 030304 developmental biology Pharmacology Complement Inactivator Proteins 0303 health sciences MESH: Humans business.industry Complement System Proteins medicine.disease Complement system Cell biology [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology Lectin pathway MESH: Myocardial Ischemia/drug therapy Immunology MESH: Myocardial Reperfusion Injury/drug therapy [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology MESH: Myocardial Reperfusion Injury/physiopathology medicine.symptom business Complement membrane attack complex Reperfusion injury Complement component 5a 030215 immunology |
| Zdroj: | Fundamental and Clinical Pharmacology Fundamental and Clinical Pharmacology, Wiley, 2001, 15 (5), pp.293-306. ⟨10.1046/j.1472-8206.2001.00040.x⟩ |
| ISSN: | 1472-8206 0767-3981 |
| DOI: | 10.1046/j.1472-8206.2001.00040.x |
| Popis: | International audience; Although reperfusion of the ischemic myocardium is an absolute necessity to salvage tissue from eventual death, it is also associated with pathologic changes that represent either an acceleration of processes initiated during ischemia or new pathophysiological changes that were initiated after reperfusion. This so‐called ‘reperfusion injury’ is accompanied by a marked inflammatory reaction, which contributes to tissue injury. In addition to the well known role of oxygen free radicals and white blood cells, activation of the complement system probably represents one of the major contributors of the inflammatory reaction upon reperfusion. The complement may be activated through three different pathways: the classical, the alternative, and the lectin pathway. During reperfusion, complement may be activated by exposure to intracellular components such as mitochondrial membranes or intermediate filaments. Two elements of the activated complement contribute directly or indirectly to damages: anaphylatoxins (C3a and C5a) and the membrane attack complex (MAC). C5a, the most potent chemotactic anaphylatoxin, may attract neutrophils to the site of inflammation, leading to superoxide production, while MAC is deposited over endothelial cells and smooth vessel cells, leading to cell injury.Experimental evidence suggests that tissue salvage may be achieved by inhibition of the complement pathway. As the complement is composed of a cascade of proteins, it provides numerous sites for pharmacological interventions during acute myocardial infarction. Although various strategies aimed at modulating the complement system have been tested, the ideal approach probably consists of maintaining the activity of C3 (a central protein of the complement cascade) and inhibiting the later events implicated in ischemia/reperfusion and also in targeting inhibition in a tissue‐specific manner. |
| Databáze: | OpenAIRE |
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