Myeloperoxidase as a marker of hemodialysis biocompatibility and oxidative stress: the underestimated modifying effects of heparin.
Myeloperoxidase (MPO) is a microbicidal and reactive species-generating enzyme. It traditionally is considered to be stored mostly within polymorphonuclear leukocytes and is strongly implicated in the pathogenesis of numerous diseases. MPO also has been studied for at least 20 years as a marker of hemodialysis procedure biocompatibility and oxidative stress generation; research yielded discordant and inconclusive results. In this review, a novel and growing body of evidence indicating that MPO also is a potent blood vessel-bound enzyme that can be mobilized rapidly and extensively into circulating blood by exogenous heparin is discussed. Beneficial consequences of such evoked arterial wall MPO depletion that may be counterbalanced in part by the harmful effects of circulating MPO on polymorphonuclear leukocyte activation and thus atherosclerosis propagation also are presented. Potential clinical implications of these undervalued phenomena in commonly atherosclerotic maintenance hemodialysis patients regularly administered large doses of heparin for temporary blood anticoagulation (frequently over years) are stressed, including the challenging issue of morbidity and mortality. In view of the plausible clinical importance of the novel MPO-oxidative stress-heparin interaction in this population, the need for additional studies assessing different dialyzer membranes, various heparin types (unfractionated heparin versus low-molecular-weight heparins versus pentasaccharides), as well as different anticoagulation regimens, is emphasized.
Borawski
Jacek
J
Department of Nephrology and Transplantology, Medical University, Białystok, Poland. jborawski@post.pl
D000925:Anticoagulants / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000201:enzymology / Q000209:etiology; D001550:Benzamidines; D001672:Biocompatible Materials / Q000009:adverse effects; D015415:Biomarkers; D001808:Blood Vessels / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006493:Heparin / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008567:Membranes, Artificial; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000032:analysis* / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects* / Q000295:instrumentation; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D001550:Benzamidines; D001672:Biocompatible Materials; D015415:Biomarkers; D006146:Guanidines; D006495:Heparin, Low-Molecular-Weight; D008567:Membranes, Artificial; D006493:Heparin; D009195:Peroxidase; C032855:nafamostat