Vascular biology of metabolic syndrome

The metabolic syndrome is a constellation of clinical risk factors comprising atherogenic dyslipidemia (low high-density lipoprotein and high triglycerides levels), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state accompanied by an increased risk for cardiovascular disease and type 2 diabetes mellitus. The adipose tissue of obese humans contains increased numbers of macrophages, and once activated, these macrophages are responsible for the expression of most of the tissue's tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Chronic inflammation associated with visceral obesity induces altered lipoprotein metabolism and insulin resistance in the liver. Adipocytes secrete a variety of hormones, cytokines, growth factors, and other bioactive substances, conceptualized as adipocytokines, including plasminogen activator inhibitor 1 (PAI-I), TNF-alpha, leptin, and adiponectin. The dysreg-ulation of these adipokines contributes to the pathogenesis of obesity. Adipose tissue-resident macrophages and adipocytes in the adipose tissue combined with the consequences of hyperglycemia, altered lipoproteins, and hyperinsulinemia in the vasculature and within organ microcirculation lead to dysfunctional endothelia and a proinflammatory state. Metabolic syndrome thus represents a combination of synergistic vascular pathologies that lead to an accelerated atherogenic state that compromises the ability of the patient to satisfactorily respond to humoral, cellular, and mechanical stresses. (J Vase Surg 2011;54:819-31.) Clinical Relevance: The incidence of metabolic syndrome is rapidly approaching epidemic levels. Cardiovascular morbidity and mortality increases 1.5-fold to 3-fold in the presence of the metabolic syndrome. Metabolic syndrome is a constellation of risk factors of metabolic origin characterized by hyperinsulinemia, low glucose tolerance, and truncal obesity. The syndrome is associated with atherogenic dyslipidemia (low high-density lipoprotein and high triglycerides levels), elevated blood pressure, elevated plasma glucose, and a prothrombotic and a proinflammatory state that act synergistically to produce a proinflammatory prothrombotic state in the vascular patient. Identifying the patient with metabolic syndrome and understanding its biology is key to developing preventive interventions and therapeutic strategies.