Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin–angiotensin system

Corry, Dalila B.; Eslami, Pirooz; Yamamoto, Kei; Nyby, Michael D.; Makino, Hírofumi; Tuck, Michael L.

doi:10.1097/hjh.0b013e3282f240bf

Cited by 671 publications

(529 citation statements)

References 27 publications

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“…Previous reports have shown that uric acid induces endothelial dysfunction and smooth muscle cell proliferation by activating the RAS and inflammatory mediators such as tumor necrosis factor-alpha and mitogen-activated protein kinases, which are known to induce cardiac hypertrophy [1,10,11,30]. It has been also reported that uric acid in vitro may increase endothelin-1 gene expression in rat cardiac fibroblasts [12].…”

Section: Discussionmentioning

confidence: 97%

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Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men

Mulè

Nardi

Costanzo

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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Background and aim: Experimentally uric acid may induce cardiomyocyte growth and interstitial fibrosis of the heart. However, clinical studies exploring the relationship between serum uric acid (SUA) and left ventricular (LV) mass yielded conflicting results.The aim of our study was to evaluate the relationships between SUA and LV mass in a large group of Caucasian essential hypertensive subjects. Methods and results: We enrolled 534 hypertensive patients free of cardiovascular complications and without severe renal insufficiency. In all subjects routine blood chemistry, including SUA determination, echocardiographic examination and 24 h ambulatory blood pressure (BP) monitoring were obtained.In the overall population we observed no significant correlation of SUA with LV mass indexed for height 2.7 (LVMH 2.7 ) (r Z 0.074). When the same relationship was analysed separately in men and women, we found a statistically significant correlation in female gender (r Z 0.27; p < 0.001), but not in males (r Z À0.042; p Z NS). When we grouped the study population in sex-specific tertiles of SUA, an increase in LVMH 2.7 was observed in the highest tertiles in women (44.5 AE 15.6 vs 47.5 AE 16 vs 55.9 AE 22.2 g/m 2.7 ; p < 0.001), but not in men.The association between SUA and LVMH 2.7 in women lost statistical significance in multiple regression analyses, after adjustment for age, 24 h systolic BP, body mass index, serum creatinine and other potential confounders. Conclusions: Our findings do not support an independent association between SUA and LV mass in Caucasian men and women with arterial hypertension. ª

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Section: Discussionmentioning

confidence: 97%

“…Indeed, uric acid is thought to induce experimentally cardiomyocyte growth and interstitial fibrosis of the heart, in part via activation of the renineangiotensin system (RAS) [10,11] and in part by inducing endothelin-1 gene expression in cardiac fibroblasts [12].…”

Section: Introductionmentioning

confidence: 99%

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men

Mulè

Nardi

Costanzo

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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“…Under normal conditions, reactive oxygen species are generated by xanthine oxidase that may impair nitric oxide production, and consequently induce endothelial dysfunction, and impair mitochondrial ATP production 33. UA may also stimulate production of C‐reactive protein, inhibit endothelial cell proliferation, which can also cause endothelial dysfunction,34 induce smooth muscle cell proliferation, and increase the production of angiotensin II 35. However, UA is excreted by the kidney.…”

Section: Discussionmentioning

confidence: 99%

Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta‐analysis

et al. 2016

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BackgroundPrevious studies have shown that xanthine oxidase inhibitors (XOI) might improve outcome for patients with cardiovascular disease. However, more evidence is required.Methods and resultsWe published a meta‐analysis of trials conducted before 2014 examining the effects of XOI on mortality in patients with cardiovascular disease. At least two further trials (N = 323 patients) have since been published. Accordingly, we repeated our analysis after a further search for randomized controlled trials of XOI in PubMed/MEDLINE, EMBASE, and Cochrane Databases. We identified eight relevant trials with 1031 patients. The average age of the patients was 61 years and 68% were men (one study did not report gender). There were 57 deaths in these eight trials, 26 in those assigned to XOI, and 31 in those assigned to the control. The updated meta‐analysis could not confirm a reduction in mortality for patients assigned to XOI compared with placebo (odds ratio 0.84) but 95% confidence intervals were wide (0.48–1.47).ConclusionsThis updated meta‐analysis does not suggest that XOI exert a large reduction in mortality but also cannot exclude the possibility of substantial harm or benefit.

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“…30 There are multiple ways in which UA can most likely cause vascular remodelling. UA can alter the proliferation and migration of vascular smooth muscle cells 31,32 by activating a series of pathways including mitogen-activated protein kinases, 32,33 platelet-derived growth factors, chemokines (monocyte chemoattractant protein-1), and inflammatory enzymes (COX-2). 32,33 Besides its possible direct effect on vascular smooth muscle cells proliferation and migration, UA may also exert other detrimental effects on the vascular system.…”

Section: Discussionmentioning

confidence: 99%

Uric acid and the cardiovascular profile of African and Caucasian men

2010

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The African population is considered a high-risk group for the development of hypertension, and identifying risk factors are therefore essential in preventive actions against cardiovascular disease (CVD). Elevated levels of uric acid (UA) are often associated with CVD. Our first aim was to establish possible ethnic differences in UA levels between African and Caucasian men. Our second aim was to determine any associations between UA levels and cardio-metabolic variables, and also how these correlates differ between the two groups. African (N ¼ 87) and Caucasian (N ¼ 121) men participated in this cross-sectional study. Our results have shown that African men had significantly lower (353±87.7 vs 401 ± 98.2; Po0.01) UA levels compared with Caucasian men. Waist circumference and triglycerides correlated strongly with UA in both ethnic groups. This was confirmed with a forward stepwise multiple regression analysis. After adjustment for confounders, the correlation between UA and triglycerides remained significant only in the Caucasians (r ¼ 0.29; P ¼ 0.02), whereas only the African men showed an independent correlation between UA and total peripheral resistance (TPR) (r ¼ 0.23; P ¼ 0.04). TPR increased significantly across UA tertiles only in the African men (P ¼ 0.01 vs P ¼ 0.96).In conclusion, despite their lower UA levels, Africans showed an independent relationship between UA and vascular resistance, indicating a possible explanation for their high prevalence of hypertension.

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Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin–angiotensin system

Cited by 671 publications

References 27 publications

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men

Absence of an independent association between serum uric acid and left ventricular mass in Caucasian hypertensive women and men

Xanthine oxidase inhibition for the treatment of cardiovascular disease: an updated systematic review and meta‐analysis

Uric acid and the cardiovascular profile of African and Caucasian men

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