Chlorinated Lipids: Vignettes on Novel Lipid Oxidation Products

Inflammation associated with ischemic heart disease, atherosclerosis, and microvascular dysfunction involves activation of leukocytes. Leukocytes activation leads to the production of hypochlorous acid through the activity of myeloperoxidase. Our lab discovered that hypochlorous acid targets host tissue plasmalogens (an abundant phospholipid in mammalian cells) leading to the production of a family of chlorinated lipids that are produced during leukocyte activation. We have investigated the role of these lipids in ischemia reperfusion injury to the heart and atherosclerosis. Chlorinated lipids accumulate in ischemic/reperfused myocardium and using isolated working hearts we have shown they decrease cardiac contractility. The mechanism responsible for this decreased contractility is an active research area in our lab. Chlorinated lipids also are elevated in human atherosclerotic plaques, and recent studies in mice suggest they are pro-atherogenic. These studies also led to some unexpected findings regarding these chlorinated lipids and mice fed a high fat diet, which will be presented in the seminar. Recent studies in our lab have focused on the role of neutrophil activation and endothelial injury. Last, the role of halogen inhalation toxicity and the role of these halogenated lipids under these conditions will be presented.