Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts

Cheng, Tzu-Hurng; Lin, Jia Wei; Chao, Hung-Hsing; Chen, Yen Ling; Chen, Cheng Hsien; Chan, Paul; Liu, Ju Chi

doi:10.1016/j.ijcard.2008.09.004

Cited by 63 publications

(50 citation statements)

References 21 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]. Indeed, a significant positive relation between SUA and LVM or LVH has been reported in some studies conducted in Asian populations [8,13e15].…”

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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“…[42][43][44] IL-6 and other chemokines in synovial fluid and synovium of RA patients have also been reported to be significantly elevated compared with control subjects. 9,28 Uric acid crystals have been shown to activate the MAPK (p38 MAPK, JNK and ERK1/2) signaling pathway in T-cell lines 20 and also activate the ERK signaling pathway in fibroblasts, 45 but the signaling pathways downstream of uric acid crystals in FLS have not been reported. We have recently reported that the inflammatory cytokine IL-27 can stimulate FLS in RA by activation of the JNK, AKT and Janus kinase signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

et al. 2011

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Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses. However, the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) have not been elucidated. Therefore, we investigated the in vitro effects of monosodium urate crystals, alone or in combination with the inflammatory cytokines tumor-necrosis factor (TNF)-a or interleukin (IL)-1b, on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals. Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6, the chemokine CXCL8 and the matrix metalloproteinase (MMP)-1 from both normal and RA-FLS (all P,0.05). Moreover, the additive or synergistic effect on the release of IL-6, CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-a or IL-1b. Further experiments showed that the release of the measured inflammatory cytokine, chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway. Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA. Keywords: cytokines; fibroblast-like synoviocytes; rheumatoid arthritis; signal transduction; uric acid INTRODUCTION Arthritis is the most common cause of joint pain and physical disability in developed countries and worldwide. 1 Gout is an acute inflammatory arthritis whose incidence has increased over the past decade, which is characterized by elevated serum urate concentrations and recurrent attacks by intra-articular uric acid crystal deposition. 2 Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis with 1% prevalence in industrialized countries, which is characterized by cytokinemediated inflammation of the synovium and destruction of cartilage and bone. 3 Uric acid crystal-mediated gouty attacks have also been observed in patients with RA. 4,5 Fibroblast-like synoviocytes (FLS) are resident mesenchymal cells in synovial joints that play crucial roles in both joint damage and the propagation of inflammation in arthritic diseases. 6 The ability of FLS to erode cartilage is a multistep process that includes the attachment of FLS onto cartilage and the synthesis of matrix metalloproteinases (MMPs) such as MMP-1. 7 Additionally, FLS secrete receptor activator of nuclear factor-kB ligand, which can attract macrophages from the vasculature, stimulate the differentiation of vascular-and tiss...

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“…Unlike the relationship between chronic elevation of uric acid and the diseases described above, it is suggested that an acute increase in serum uric acid may have beneficial effects. According to studies, giving uric acid externally to those with normal levels of uric acid increases the plasma antioxidant capacity and restores endothelial function in those with type 1 diabetes and those who smoke regularly (17). Uric acid in humans neutralizes oxidative damage related to aging and atherosclerosis.…”

Section: Clinical Significancementioning

confidence: 99%

Analysis of Uric Acid Elevation

Ayyıldız¹

2016

JAREM

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Uric acid is a molecule that is produced following purine nucleotide metabolism. It is particularly synthesized in the liver and less often in other tissues. In normal concentrations, it is an antioxidant and a proinflammatory; however, if its serum concentration is over 7.0 mg/dL, it immediately crystalizes and precipitates, particularly in the vessel walls, soft tissues, joints, and renals. Several studies have demonstrated that there a positive relationship between hyperuricemia and diseases such as metabolic syndrome, stroke, preeclampsia, hypertension, kidney diseases, cardiovascular diseases, and diabetes mellitus. Identification of the elevated uric acid concentration and early treatment of hyperuricemia may help in early diagnosis and treatment of diseases that are positively related to hyperuricemia. Thus, serum uric acid concentrations should be well examined during biochemical analyses of patients visiting the hospital. In this review, uric acid and its elevated concentrations were re-checked and its importance in health was emphasized. (JAREM 2016; 6: 74-7)

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Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts

Cited by 63 publications

References 21 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

Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

Analysis of Uric Acid Elevation

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