Therapeutic Lifestyle Changes Improve HDL Function by Inhibiting Myeloperoxidase-Mediated Oxidation in Patients With Metabolic Syndrome

Abstract

OBJECTIVE Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated oxidative stress remains unclear. RESEARCH DESIGN AND METHODS In this study, we characterized changes in cholesterol efflux capacity (CEC), a metric of HDL function; MPO-mediated oxidation; and the HDL proteomic profile in 25 patients with MetS who underwent 12 weeks of TLCs. RESULTS After 12 weeks, before significant changes to HDL levels, most MetS components improved as a result of the TLCs. CEC was significantly increased, and HDL MPO oxidation products, 3-chlorotyrosine and 3-nitrotyrosine, were decreased with TLCs. The changes in CEC were inversely related to the unit changes in 3-chlorotyrosine after we controlled for changes in the other MetS components. TLCs did not remodel the HDL proteome. CONCLUSIONS In summary, TLCs improved HDL function by inhibiting MPO-mediated oxidative stress even before appreciable changes in HDL levels.