Abstract. Hyperuricemia appears to be associated with an increased risk for cardiovascular disease and associated mortality. Population epidemiological data support a causal link between hyperuricemia and cardiovascular disease. Endothelium injury could be one of the potential mechanisms in hyperuricemia-induced cardiovascular disease. However, the specific role of uric acid (UA) in the impairment of vascular relaxation and its signal transduction pathway has not been examined. The authors investigated the role of UA on vascular relaxation, nitric oxide (NO) production and expression of proinflammatory cytokines. Brachial flow-mediated dilation and nitroglycerine-mediated dilation were measured by B-mode ultrasound with 10 megahertz linear-array transducer from 21 patients with hyperuricemia and 16 control subjects. Human umbilical vein endothelial cells (ECs) were incubated with UA (5-15 mg/dl) with or without nuclear factor (NF)-κB inhibitor II. Hyperuricemia inhibited brachial flow-mediated dilation. While UA significantly inhibited NO expression with time course-and dose-dependent manner in the cultured ECs, 10 mg/dl UA also increased expression of inflammation cytokine interleukin (IL)-6, IL-8 and tumor necrosis factor-α in vitro. These abnormalities were associated with UA-induced activation of transcription factor NF-κB. Furthermore, NF-κB inhibitor II prevented UA-induced reduction of NO and increased inflammation cytokines. These data suggested hyperuricemia-induced endothelium injury and vascular dysfunction by a reduction of NO and expression of inflammatory cytokines through the NF-κB pathway. IntroductionHyperuricemia has been linked to cardiovascular disease (CVD) recent since it is regarded as an independent risk factors in the contribution of CVD including vascular disease, hypertension, metabolic syndrome and renal disease (1). Generally, uric acid (UA) levels >7 mg/dl in males and >6 mg/dl in females are considered as hyperuricemia in a clinical aspect (2). Risk factors for hyperuricemia include alcohol consumption, intake of high fat diet and refined carbohydrate, and the medicines of diuretics and angiotensin converting enzyme antagonists (1,2). Population epidemiological studies support the notion that there is a causal link between hyperuricemia and CVD. For example, Rotterdam (3) and a NHANES I study (4) found that there is an association between high levels of UA and myocardial infarctions and cardiovascular death even after adjustment for related factors such as age, dyslipidemia and obesity. Multiple center studies also suggested that hyperuricemia prompts hypertension and coronary heart disease, as well as vascular diseases such as cerebrovascular disease, preeclampsia, vascular dementia and kidney disease (5,6). Some of the potential pathophysiological mechanisms have been investigated to explain the association between UA and vascular injury. One study suggested that high dose UA significantly increased angiotensin II and oxidative stress in cultured endothelial cells (ECs) and this ...
Based on the number of protons and electrons in the existing element, this paper believes that the electron configuration of the element needs to be changed in order to obtain its new properties and principle of electron pairing. The new electron configuration is the square of the number of periods. The first, second, third, and fourth periods contain 1, 4, 9, and 16 electrons respectively. Atoms evolve by the movement of electrons from the outer core, attracting electrons from different atoms to form compounds. When low hierarchy elements combine with high hierarchy ones, their electrons preferentially choose electrons of higher period of each other for coordination. So H atomic electrons are more likely to attract and pair with electrons of the second period of C, N and O to form bonds, while the outermost electron of O in the third period tends to pair with electrons in the fourth period of P, S and Cl. Then the special structure of ammonia and water molecules can be deduced, and the double bond characteristics of highpriced acids of P, S and Cl can also be explained. New periodic table of elements makes it easy and convenient to explain chemical phenomena and facilitate the understanding of the micro world.
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