Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems

Xiang, Wei; Kong, Juan; Chen, Songcang; Cao, Li; Qiao, Guilin; Zheng, Wei; Liu, Wenhua; Li, Xinmin; Gardner, David G.; Li, Yan Chun

doi:10.1152/ajpendo.00224.2004

Cited by 502 publications

(378 citation statements)

References 41 publications

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“…It has been previously reported that left ventricular hypertrophy in hemodialysis patients is associated with lower survival (37). Interestingly, there is also experimental evidence that VDR gene deletion may induce myocardial hypertrophy and fibrosis (38). The absence of vitamin D-mediated signal transduction and genomic activation reportedly results in cardiomyocyte overstimulation and increased contractility, which ultimately lead to cardiomyocyte hypertrophy (39,40).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

Barreto¹,

Barreto²,

Liabeuf³

et al. 2009

Clinical Journal of the American Society of Nephrology

142

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Results: There was a high prevalence of vitamin D deficiency (42%) and insufficiency (34%). Patients with 25D < 16.7 ng/ml (median) had a significantly lower survival rate than patients with 25D >16.7 ng/ml (mean follow-up, 605 ؎ 217 d; range, 10 to 889; P ‫؍‬ 0.05). Multivariate adjustments (included age, gender, diabetes, arterial pressure, CKD stage, phosphate, albumin, hemoglobin, aortic calcification score and PWV) confirmed 25D level as an independent predictor of all-cause mortality.Conclusions: Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort. Low 25D levels affected mortality independently of vascular calcification and stiffness, suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

Barreto¹,

Barreto²,

Liabeuf³

et al. 2009

Clinical Journal of the American Society of Nephrology

142

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“…Increased activation of the cardiac RAS system was observed in VDR knockout mice and has been linked to the development of myocardial hypertrophy [20]. In detail, Xiang et al showed that cardiac renin mRNA was significantly increased in mice lacking the VDR [20]. [21].…”

Section: Vitamin D Effects On the Cardiac Rasmentioning

confidence: 99%

Vitamin D deficiency and myocardial diseases

Pilz

Tomaschitz

Drechsler

et al. 2010

Molecular Nutrition Food Res

123

141

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Vitamin D deficiency is common among patients with myocardial diseases because sun-induced vitamin D production in the skin and dietary intake of vitamin D is often insufficient. Knockout mice for the vitamin D receptor develop myocardial hypertrophy and dysfunction. It has also been shown that children with rickets who suffered from severe heart failure could be successfully treated with supplementation of vitamin D plus calcium. In adults, almost all patients with heart failure exhibit reduced 25-hydroxyvitamin D levels, which are used to classify the vitamin D status. In prospective studies, vitamin D deficiency was an independent risk factor for mortality, deaths due to heart failure and sudden cardiac death. Several vitamin D effects on the electrophysiology, contractility, and structure of the heart suggest that vitamin D deficiency might be a causal factor for myocardial diseases. Data from interventional trials, however, are rare and urgently needed to elucidate whether vitamin D supplementation is useful for the treatment of myocardial diseases. In our opinion, the current knowledge of the beneficial effects of vitamin D on myocardial and overall health strongly argue for vitamin D supplementation in all vitamin D-deficient patients with or at high risk for myocardial diseases.

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“…Dietary phosphate restriction can significantly lower FGF-23 levels [53][54][55] and could be more effective if started before serum phosphate levels increase. Vitamin D receptor agonists may effectively inhibit both the TGF-␣-converting enzyme/TGF␣/EGF receptor pathway and the RAAS in the parathyroid and kidney 90,91 and reduce vascular calcification, podocyte damage, 63,[92][93][94] and proteinuria through blockade of Wnt/␤-catenin signaling. 95 Vitamin D receptor agonists also may upregulate klotho 96 and exert an antiinflammatory action through the reduction of nuclear factor B.…”

Section: Insights From Recent Experimental Studies and Novel Therapeumentioning

confidence: 99%

Blood Pressure, Proteinuria, and Phosphate as Risk Factors for Progressive Kidney Disease: A Hypothesis

Cozzolino

Gentile

Mazzaferro

et al. 2013

American Journal of Kidney Diseases

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Chronic kidney disease (CKD) affects approximately 500 million people worldwide and is increasingly common in both industrialized and emerging countries. Although the mechanisms underlying the inexorable progression of CKD are incompletely defined, recent discoveries may pave the way to a more comprehensive understanding of the pathophysiology of CKD progression and the development of new therapeutic strategies. In particular, there is accumulating evidence indicating a key role for the complex and yet incompletely understood system of divalent cation regulation, which includes phosphate metabolism and the recently discovered fibroblast growth factor 23 (FGF-23)/klotho system, which seems inextricably associated with vitamin D deficiency. The aim of this review is to discuss the links between high blood pressure, proteinuria, phosphate levels, and CKD progression and explore new therapeutic strategies to win the fight against CKD. Am J Kidney Dis. xx(x):xxx. © 2013 by the National Kidney Foundation, Inc. INDEX WORDS:Chronic kidney disease; vitamin D deficiency; blood pressure; proteinuria; phosphate.C hronic kidney disease (CKD) is a silent killer.Four of 5 people with advanced CKD are not aware of the disease until death is imminent and kidney replacement therapy (dialysis or kidney transplantation) is unavoidable. Unfortunately, Ͻ10% of people requiring replacement therapy have access to it, and more than 1 million people worldwide die of untreated kidney failure each year because dialysis or kidney transplantation is unaffordable in most countries. This represents a huge economic burden, with global costs from 2000-2010 surpassing $1 trillion. 1,2 Worsening kidney function is associated with a marked increase in cardiovascular morbidity and mortality 1,3 independent of other risk factors. Coexistent hypertension is present in ϳ80% of patients with CKD and worsens cardiovascular outcomes because only 64% of patients with CKD achieve adequate blood pressure control. 4 As a consequence, only a minority of the hundreds of thousands of patients with stages 3 and 4 CKD reach kidney failure. 5 Proteinuria also is an important prognostic factor in patients with CKD. Although patients with nonproteinuric CKD are at greater risk of cardiovascular mortality than progression to kidney failure, the opposite may be true for the presence of proteinuria. Patients from the REIN (Ramipril Efficacy in Nephropathy) Study who were in the highest tertile of baseline proteinuria (protein excretion Ն3.8 g/d) also experienced the highest rate of glomerular filtration rate (GFR) loss during followup. 6 In addition, although post hoc analysis of RENAAL (Reduction of Endpoints in NIDDM [Non-InsulinDependent Diabetes Mellitus] With the Angiotensin II Antagonist Losartan) showed that 85% of patients with proteinuria with protein excretion Ն3 g/d reached the composite end point of doubling of serum creatinine level or end-stage renal disease (ESRD), only 44% of these patients reached the composite cardiovascular outcome. 7 Besides the we...

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Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems

Cited by 502 publications

References 41 publications

Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

Vitamin D Affects Survival Independently of Vascular Calcification in Chronic Kidney Disease

Vitamin D deficiency and myocardial diseases

Blood Pressure, Proteinuria, and Phosphate as Risk Factors for Progressive Kidney Disease: A Hypothesis

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