Oxidative stress and vascular implications in metabolic syndrome. Metabolic syndrome (MS) is characterized by risk factors having tissue oxidative stress (OS) as hallmark. Indeed, they are characterized by increased release and accumulation of proinflammatory mediators, such as free fatty acids (FFAs), high glucose levels, advanced glycation end-products (AGE), cytokines, and angiotensin II, as well as to the activation proinflammatory signals linked to the stimulation of protein kinase C (PKC) and polyol pathways. These conditions boost the increase in reactive oxygen (ROS) and nitrogen species (RNS) formation in tissues and in the vasculature through the activation of the related producing enzymes in the cytosol as well as in the mitochondria. The cytosolic enzymes include the different isoforms of NADPH oxidase (NOXs), nitric oxide synthase (NOS), cyclooxygenase (COX), xanthine oxidase, protein kinase C (PKC), uncoupled endothelial NOS (eNOS), and myeloperoxidase (MPO). Other potential sources of ROS and RNS are the oxidized RBCs (oxRBCs) and the increased NADH amounts. The former, forming in the vasculature under significant OS conditions, behave as prooxidant cells able also to release oxidant species. The latter, increased at expenses of NADPH under hyperglycemic conditions, can induce mitochondrial deregulation and ROS formation. Noteworthy for the MS-associated cardiovascular complications is the reduction in •NO bioavailability in the vasculature, notwithstanding the NOS upregulation. Indeed, the simultaneous increase in the concentration of •NO and O2• allows these radicals to react fast generating the strong oxidant peroxynitrite (ONOO-), which deeply affects intracellular redox chemistry. The MS-associated diseases are also characterized by the downregulation of the antioxidant systems, including the depletion of GSH concentration and the decrease of the activity of the detoxifying enzymes, such as superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (Gpx), glutathione reductase (GR), and the couple constituted by thioredoxin (Trx) and thioredoxin reductase (TrxR). In addition, as in a vicious cycle, the increased ROS and RNS formation can further worse MS-related diseases by affecting in turn the intracellular pathway generating the proinflammatory mediators, as well as decrease the activity of the antioxidant systems. All these conditions result in the irreversible accumulation of oxidation products in proteins, lipids, and sugars, which allow the impairment of intracellular redox signaling and detrimentally affect vascular biology by promoting vascular inflammation, endothelial dysfunction, and vascular remodeling. These alterations underlie the typical MS-associated cardiovascular complications, such as coronary atherosclerotic disease, arterial hypertension, left ventricular hypertrophy, diastolic dysfunction, coronary microvascular disease, and autonomic dysfunction.