Dysregulation of monocyte biology in metabolic syndrome

Metabolic syndrome (MetS), which constitutes a cardio-metabolic risk cluster, is becoming a global epidemic. It is a pro-inflammatory and pro-oxidant state that confers an increased risk of cardiovascular disease and diabetes. MetS is not only characterized by increased circulating biomarkers of inflammation and oxidative stress but also by dysregulation of a pivotal phagocyte, the circulating monocyte. Pertubations manifesting in monocytes of patients with MetS include increased Toll-like receptors, CD40-CD40L dyad, increased ER stress, increased CCR5 and Fc-γ receptors (CD32 and CD64). Additionally, the monocytes demonstrate increase in NADPH oxidase activity and decreased Nrf2, resulting in oxidative damage to biomolecules. Thus the dysregulated monocyte in MetS appears to be a critical cell in the predisposition of MetS patients to diabetes and CVD. Therapeutic strategies targeting monocytes can attenuate this risk and the most compelling data derives from studies with statin therapy.