Increased circulating trimethylamine N-oxide contributes to endothelial dysfunction in a rat model of chronic kidney disease

Li, Tiejun; Gua, Chaojun; Wu, Baogang; Yan-li, Chen

doi:10.1016/j.bbrc.2017.12.069

Cited by 64 publications

(55 citation statements)

References 35 publications

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“…Accordingly, upregulated TMAO levels were showed to be independently associated with renal dysfunction (eGFR < 60 ml/min/1.73m 2 ) after adjustment for sex, age, SBP, HbA1c, TG, HDL and LDL by logistic regression in the present study. In experimental mice models, Li demonstrated the contributory role of TMAO in the pathogenesis of endothelial dysfunction and CKD [32]. Here we expand those findings by revealing the risk predicting power of TMAO in HFpEF patients with impaired renal function compared to those with normal renal function (AUC = 0.67, p < 0.01, best cut-off = 8.48 μg/l, Fig.…”

Section: Discussionsupporting

confidence: 67%

Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction

Guo

Qiu

Tan

et al. 2020

BMC Cardiovasc Disord

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Background: Heart failure with preserved ejection fraction (HFpEF) is an emerging global health problem with less awareness. Renal dysfunction in HFpEF is associated with worse outcome. However, there is lack of rapid, noninvasive and accurate method for risk stratification in HFpEF and renal dysfunction. This study aimed to explore the utility of plasma trimethylamine n-oxide (TMAO) for evaluation of HFpEF and renal function. Methods: Plasma TMAO levels were measured in total 324 subjects comprising 228 HFpEF patients and 96 healthy controls. Results: TMAO levels were significantly elevated in patients with HFpEF compared with controls (12.65(9.32-18.66) μg/l vs 10.85(6.35-15.58) μg/l, p < 0.01). Subjects in higher TMAO tertile group had more incidences of HFpEF ((78.5%) in tertile 3 vs (73.39%) in tertile 2 vs (59.26%) in tertile 1, p < 0.01). TMAO concentrations were inversely correlated with estimated glomerular filtration rate (eGFR) and HFpEF patients with impaired renal function (eGFR < 60 ml/min/1.73 m 2) had higher TMAO than those with normal eGFR (≥ 60 ml/min/1.73 m 2) (14.18(10.4-23.06) μg/l vs 10.9(7.48-15.47) μg/l, p < 0.01). Increased TMAO levels were independently associated with higher risk of HFpEF (OR = 3.49, 95% CI: 1.23-9.86, p = 0.02) and renal dysfunction (OR = 9.57, 95% CI: 2.11-43.34, p < 0.01) after adjustment for multiple traditional risk factors. Furthermore, TMAO had good performance at distinguishing HFpEF from controls (AUC = 0.63, p < 0.01), and renal dysfunction from normal renal function in HFpEF (AUC = 0.67, p < 0.01). Conclusion: In this cross-sectional study, HFpEF and renal function were closely related with plasma TMAO levels and TMAO may serve as a diagnostic biomarker for HFpEF and renal function.

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Section: Discussionsupporting

confidence: 67%

Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction

Guo

Qiu

Tan

et al. 2020

BMC Cardiovasc Disord

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“…Recent evidence supports the notion that increased TMAO concentration contributes to the promotion of cardiac dysfunction and atherosclerosis ( Fig. 2 and 3) (Al-Rubaye et al, 2019;Kanitsoraphan et al, 2018;Koeth et al, 2013;Li et al, 2018;Randrianarisoa et al, 2016;Stremmel et al, 2017;Tang et al, 2015;Velasquez et al, 2016;Nam, 2019). Atherosclerosis is a chronic inflammatory disease.…”

Section: The Mechanistic Role Of Tmao In the Pathogenesis Of Atheroscsupporting

confidence: 60%

Diet-induced chronic syndrome, metabolically transformed trimethylamine-N-oxide, and the cardiovascular functions

Hardin

Singh

Eyob

et al. 2019

Rev. Cardiovasc. Med.

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Recent studies have shown that the integrity of the gastrointestinal tract and its microbiome impact the functioning of various body systems by regulating immunological responses, extracting energy, remodeling intestinal epithelia, and strengthening the gut itself. The gastrointestinal tract microbiota includes bacteria, fungi, protozoa, viruses, and archaea which collectively comprise a dynamic community prone to alterations via influences such as the environment, illness, and metabolic processes. The idea that the host's diet possesses characteristics that could potentially alter microbiota composition is a novel notion. We hypothesize that a high fat diet leads to the alteration of the gastrointestinal microbiota composition and that metabolic transformation of the compound trimethylamine into trimethylamine-N-oxide promotes vasculopathy such as atherosclerosis and affects cardiovascular functionality. Furthermore, we hypothesize that treatment with probiotics will restore the homeostatic environment (eubiosis) of the gastrointestinal tract.

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“…Impaired endothelial function has been extensively studied in patients with CKD, and is considered as a major player in the detrimental interactions between the kidney and the cardiovascular system in CKD 37 . Endothelial dysfunction after 5/6 Nx has previously been shown in rat models of CKD 38 . In mice models of CKD impaired flow-mediated vasodilation in a resistance vessel had not been reported previously, while this is generally considered as a gold-standard method to demonstrate and study endothelial dysfunction.…”

Section: Compared 5/6mentioning

confidence: 78%

5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice

Hamzaoui

Djerada

Brunel

et al. 2020

Sci Rep

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Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. Twelve weeks after 5/6 Nx, CKD was demonstrated by a significant increase in plasma creatinine in both 129/ Sv and C57BL/6JRj male mice. Polyuria and kidney histological lesions were more pronounced in 129/Sv than in C57BL/6JRj mice. Increase in albuminuria was significant in 129/Sv but not in C57BL/6JRj mice. Both strains exhibited an increase in systolic blood pressure after 8 weeks associated with decreases in cardiac systolic and diastolic function. Heart weight increased significantly only in 129/Sv mice. Endothelium-dependent mesenteric artery relaxation to acetylcholine was altered after 5/6 Nx in C57BL/6JRj mice. Marked reduction of endothelium-dependent vasodilation to increased intraluminal flow was demonstrated in both strains after 5/6 Nx. Cardiovascular and kidney consequences of 5/6 Nx were more pronounced in 129/Sv than in C57BL/6JRj mice. Chronic kidney disease (CKD) is a major health problem, with a worldwide prevalence of 13% 1. A strong association has been demonstrated between the decrease in glomerular filtration rate (GFR), the risk of developing functional and structural disorders of the heart and cardiovascular (CV) events 2-4. Accordingly, CV disease represents the leading cause of mortality in this population. Multiple mechanisms lead to the CV consequences of CKD, and endothelial dysfunction is considered as a cornerstone in this setting 5,6. Due to limited pathophysiological understanding, a large amount of research is currently dedicated to the deleterious reciprocal interactions of heart and kidney diseases, within the 5 types of cardiorenal syndrome 7. Different models of CKD have been developed in rodents, including kidney mass reduction by 5/6 nephrectomy (5/6 Nx), DOCA salt nephropathy, unilateral ureteral obstruction, oxalate-induced CKD, adenine-induced CKD and genetic mutation of Col4A3 8-12 , but these models do not fully reproduce the CV consequences of CKD observed in humans, including coronary heart disease. 5/6 Nx has been widely used in rats 13,14 because of the persistent decrease in GFR, proteinuria, glomerular sclerosis and hypertension induced, contributing to the major interest of this model 15. To date, several factors, including surgical difficulties, have limited the use of 5/6 Nx in mice 16. This is of critical importance in particular because transgenic mice, most commonly developed on a C57BL/6JRj background, currently represent a key experimental tool. In the literature reporting results of 5/6 Nx in mice, strain-dependent differences appear regarding hypertension, alb...

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Increased circulating trimethylamine N-oxide contributes to endothelial dysfunction in a rat model of chronic kidney disease

Cited by 64 publications

References 35 publications

Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction

Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction

Diet-induced chronic syndrome, metabolically transformed trimethylamine-N-oxide, and the cardiovascular functions

5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice

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