Neutrophil-mediated accumulation of 2-ClHDA during myocardial infarction: 2-ClHDA-mediated myocardial injury.
The pathophysiological sequelae of myocardial infarction include neutrophil infiltration into the infarct zone that contributes to additional damage to viable tissue and removal of cellular debris from necrosed tissue. Reactive chlorinating species produced by myeloperoxidase amplify the oxidant capacity of activated neutrophils. Plasmalogens are a major phospholipid subclass of both endothelial cells and cardiac myocytes. Recent studies have shown that plasmalogens are targeted by neutrophil-derived reactive chlorinating species that lead to the production of alpha-chloro fatty aldehydes. Results herein demonstrate that the alpha-chloro fatty aldehyde 2-chlorohexadecanal (2-ClHDA) accumulates in rat hearts subjected to left anterior descending coronary artery occlusion. Myocardia from rats subjected to surgical infarction had increased 2-ClHDA and neutrophil infiltration levels compared with myocardia from rats subjected to sham surgery. Additionally, infarcted myocardia from rats rendered neutropenic by treatments with an anti-neutrophil antibody had diminished 2-ClHDA and neutrophil infiltration levels compared with infarcted myocardia from normopenic rats; 2-ClHDA was shown to elicit myocardial damage as determined by lactate dehydrogenase release in isolated perfused rat hearts. Additionally, 2-ClHDA treatment of hearts resulted in decreased heart rate and ventricular performance. Taken together, the present results demonstrate a novel neutrophil-dependent myeloperoxidase-based mechanism that results in 2-ClHDA production in response to regional myocardial infarction that may also contribute to cardiac dysfunction.
Thukkani
Arun K
AK
Dept. of Biochemistry and Molecular Biology, St. Louis Univ. School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Martinson
Bradley D
BD
Albert
Carolyn J
CJ
Vogler
George A
GA
Ford
David A
DA
D000447:Aldehydes / Q000097:blood* / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
C432398:2-chlorohexadecanal; D000447:Aldehydes