Lipid oxidation by hypochlorous acid: chlorinated lipids in atherosclerosis and myocardial ischemia

摘要

Leukocytes, containing myeloperoxidase (MPO), produce the reactive chlorinating species, HOCI, and they have important roles in the pathophysiology of cardiovascular disease. Leukocyte-derived HOCI can target primary amines, alkenes and vinyl ethers of lipids, resulting in chlorinated products. Plasmalogens are vinyl ether-containing phospholipids that are abundant in tissues of the cardiovascular system. The HOCI oxidation products derived from plasmalogens are a-chlorofatty aldehyde and unsaturated molecular species of lysophosphatidylcholine. a-chlorofatty aldehyde is the precursor of both a-chlorofatty alcohol and a-chlorofatty acid. Both a-chlorofatty aldehyde and a-chlorofatty acid accumulate in activated neutrophils and have disparate chemotactic properties. In addition, a-chlorofatty aldehyde increases in activated monocytes, human atherosclerotic lesions and rat infarcted myocardium. This article addresses the pathways for the synthesis of these lipids and their biological targets.