Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol 14:164

BMC Nephrology (Impact Factor: 1.69). 07/2013; 14(1):164. DOI: 10.1186/1471-2369-14-164
Source: PubMed


Uric acid is the end product of purine metabolism in humans. High levels are causative in gout and urolithiasis. Hyperuricaemia has also been implicated in the pathophysiology of hypertension, chronic kidney disease (CKD), congestive heart failure (CHF), the metabolic syndrome, type 2 diabetes mellitus (T2DM), and atherosclerosis, with or without cardiovascular events. This article briefly reviews uric acid metabolism and summarizes the current literature on hyperuricaemia in cardiovascular disease and related co-morbidities, and emerging treatment options.

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    • "Hyperuricemia is a well-known prelude to the development of many conditions, including gout and kidney disease [13]. Uric acid levels, highly predictive of body mass index (BMI) in humans, are elevated by many factors, including high purine diets and high fructose diets [10] [14]. While uric acid is a potent antioxidant, it can be highly damaging at elevated levels as seen in gout [15]. "
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    ABSTRACT: Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBP α , PPAR γ , and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.
    International Journal of Stem Cells 06/2015; DOI:10.1155/2016/8197325
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    • "A high concentration of serum uric acid (SUA) is the main cause of gout, and is also associated with the metabolic syndrome, including hypertension and diabetes mellitus (DM) [1-3]. In the report of the US National Health and Nutrition Examination Survey, among patients with gout, 74% had hypertension and 26% had diabetes [4]. "
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    ABSTRACT: Angiotensin II type 1 receptor blockers (ARB) are a frequently used class of antihypertensive drug. The ARB losartan is known to decrease the serum uric acid (SUA) level. However, there are very few clinical data comparing the effects of other ARBs on SUA level under the conditions of clinical practice. This study evaluated and compared the long-term effects of monotherapy with five ARBs on SUA level in Japanese hypertensive patients with type 2 diabetes mellitus (DM). We identified hypertensive patients with type 2 DM who had been treated with monotherapy with losartan (n = 214), valsartan (n = 266), telmisartan (n = 185), candesartan (n = 458), or olmesartan (n = 192), in whom laboratory data of SUA between November 1, 2004 and July 31, 2011 were available, from the Nihon University School of Medicine's Clinical Data Warehouse (NUSM's CDW). We used a propensity-score weighting method and a multivariate regression model to adjust for differences in the background among ARB users, and compared the SUA level. The mean exposure of losartan was 264.7 days, valsartan 245.3 days, telmisartan 235.9 days, candesartan 248.9 days, and olmesartan 234.5 days. In losartan users, mean SUA level was significantly decreased from baseline, while it was conversely increased in users of other ARBs; valsartan, telmisartan, candesartan, and olmesartan. The mean reduction of SUA level from baseline was significantly greater in losartan users compared with that in other ARB users. Comparison of ARBs other than losartan showed no significant difference in mean change in SUA level from baseline. Our study showed that losartan had the most beneficial effect on SUA level among five ARBs, and that there was no significant difference in the unfavorable effects on SUA level among four ARBs other than losartan, at least during one year. These findings provide evidence of an effect of ARBs on SUA level, and support the benefit of the use of losartan in hypertensive patients with type 2 DM.
    Cardiovascular Diabetology 11/2013; 12(1):159. DOI:10.1186/1475-2840-12-159 · 4.02 Impact Factor
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    International Journal of Nephrology and Renovascular Disease 12/2013; 6:269-270. DOI:10.2147/IJNRD.S55750
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