Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage

Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) hypothiocyanous (HOSCN) from competing substrates chloride thiocyanate. MPO overproduction of HOCl are strongly linked with vascular cell dysfunction inflammation in atherosclerosis. highly reactive causes marked death, whereas data HOSCN conflicting, dependent on nature type. In this study we have examined reactivity human coronary artery smooth muscle (HCASMC), given key role type maintaining function. reacts rapidly cells, resulting extensive death both necrosis apoptosis, increased levels intracellular calcium. contrast, more slowly, occurring only after prolonged incubation, absence accumulation Exposure HCASMC to also influences mitochondrial respiration, decreases glycolysis, lactate release, production ATP, cellular thiols glutathione levels. These changes occurred varying extents exposure HOSCN, where evidence was obtained for reversible modification thiols. induced alterations mRNA expression multiple inflammatory phenotypic genes. Interestingly, extent these specific donor used, effects observed isolated diseased compared healthy vessels. Overall, provide new insight into pathways promoting during chronic inflammation, support use thiocyanate as a means modulate MPO-induced damage