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)-α 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-1), TNF-α, leptin, and adiponectin. The dysregulation 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.