Circulating adiponectin concentrations are reduced in obese individuals, and this reduction has been proposed to have a crucial role in the pathogenesis of atherosclerosis and cardiovascular diseases associated with obesity and the metabolic syndrome. We focus on the effects of adiponectin on glucose and lipid metabolism and on the molecular anti-atherosclerotic properties of adiponectin and also discuss the factors that increase the circulating levels of adiponectin. Adiponectin reduces inflammatory cytokines and oxidative stress, which leads to an improvement of insulin resistance. Adiponectin-induced improvement of insulin resistance and adiponectin itself reduce hepatic glucose production and increase the utilization of glucose and fatty acids by skeletal muscles, lowering blood glucose levels. Adiponectin has also β cell protective effects and may prevent the development of diabetes. Adiponectin concentration has been found to be correlated with lipoprotein metabolism; especially, it is associated with the metabolism of high-density lipoprotein (HDL) and triglyceride (TG). Adiponectin appears to increase HDL and decrease TG. Adiponectin increases ATP-binding cassette transporter A1 and lipoprotein lipase (LPL) and decreases hepatic lipase, which may elevate HDL. Increased LPL mass/activity and very low density lipoprotein (VLDL) receptor and reduced apo-CIII may increase VLDL catabolism and result in the reduction of serum TG. Further, adiponectin has various molecular anti-atherosclerotic properties, such as reduction of scavenger receptors in macrophages and increase of cholesterol efflux. These findings suggest that high levels of circulating adiponectin can protect against atherosclerosis. Weight loss, exercise, nutritional factors, anti-diabetic drugs, lipid-lowering drugs, and anti-hypertensive drugs have been associated with an increase of serum adiponectin level.

Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post-reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus 9

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Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.

High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.