Neutrophil extracellular traps as a source of high density lipoprotein oxidation in lupus-related cardiovascular disease. (HUM1P.312)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.52-52.12
• Main Authors: Smith, Carolyne, Vivekanandan-Giri, Anuradha, Pennathur, Subramaniam, Kaplan, Mariana
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.52.12

Lupus patients are fifty times more likely to experience a cardiovascular event, such as stroke or myocardial infarction, compared to age- and sex-matched controls. This is not explained by traditional “Framingham” risk factors, such as obesity and smoking, but possibly by the presence of “proinflammatory”, oxidized high density lipoprotein (HDL). Enzymatic sources of HDL oxidation include myeloperoxidase (MPO) and nitric oxide synthase (NOS), two enzymes which our group has found highly present in neutrophil extracellular traps (NETs). NET structures, composed of chromatin and antimicrobial peptides, are produced by granulocytes under pathogen stimulation or spontaneously in lupus patients. It was therefore predicted that NETs, highly active in lupus patients, can transform HDL into an oxidized form which is linked to proinflammatory and proatherosclerotic pathways. We examined the levels of chloro- and nitro-tyrosine oxidation in HDL from lupus patients and control donors via tandem mass spectroscopy. Finally, we digested lupus and control granulocyte NETs and incubated this with unoxidized HDL in the absence or presence of MPO and NOS-specific inhibitors. Lupus patients exhibited higher levels of regiospecific HDL oxidation versus control. Active NOS and MPO from NETs induced HDL oxidation patterns linked with cardiovascular disease (CVD). This represents a completely unexplored cellular source of HDL oxidation for lupus associated CVD.