1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter

Yuan, Weiping; Wei, Pan; Kong, Juan; Zheng, Wei; Szeto, Frances L.; Wong, Kari E.; Cohen, Ronald N.; Kłopot, Anna; Zhang, Zhongyi; Li, Yan Chun

doi:10.1074/jbc.m705495200

Cited by 435 publications

(380 citation statements)

References 47 publications

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“…In detail, Xiang et al showed that cardiac renin mRNA was significantly increased in mice lacking the VDR [20]. [21]. Notably, renin expression is usually induced by cAMP binding to protein kinase A.…”

Section: Vitamin D Effects On the Cardiac Rasmentioning

confidence: 99%

“…1,25(OH)2D was shown to increase the Ca 21 uptake in cardiac ventricular cells. This uptake was mediated by nongenomic effects leading to the opening of Ca 21 channels, and by genomic effects requiring the de novo synthesis of proteins related to Ca 21 cycling in the myocardium [32][33][34]. 1,25(OH)2D effects on cardiac contractility and intracellular calcium handling were studied in adult rat cardiomyocytes [35].…”

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

“…The main finding was an accelerated relaxation in response to acute (5-60 min) and sustained (for at least 2 days) administration of calcitriol [35]. It was shown that protein kinase C mediated the phosphorylation of Troponin T, which decreases myofilament Ca 21 sensitivity, and of phospholamban, which increases Ca 21 sequestration into the sarcoplasmatic reticulum. These effects are mainly responsible for the acute (nongenomic) effects of calcitriol on myocardial contractility [35].…”

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

“…These pathways involve the activation of the adenylatcylase by receptor coupled G proteins [36][37][38][39][40]. Subsequent increases of cAMP activate protein kinase A, which phosphorylates subunits of the L-type Ca 21 channel, lead to increased calcium influx into the cardiomyocytes [36][37][38][39][40].…”

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

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Vitamin D deficiency and myocardial diseases

Pilz

Tomaschitz

Drechsler

et al. 2010

Molecular Nutrition Food Res

134

142

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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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Section: Vitamin D Effects On the Cardiac Rasmentioning

confidence: 99%

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

Section: Vitamin D Effects On Cardiac Contractility and Calcium Handlingmentioning

confidence: 99%

See 2 more Smart Citations

Vitamin D deficiency and myocardial diseases

Pilz

Tomaschitz

Drechsler

et al. 2010

Molecular Nutrition Food Res

134

142

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“…Likely explanations of these negative outcomes are the use of different vit D dose regimens, attempted correlations with 25OHD instead of active hormone plasma levels, the effect of renal replacement therapy, and the possible impact of other pathophysiological pathways that are related with vit D. Among the latter, the reninangiotensin-aldosterone system (RAAS) stands out as a crucial regulator of intravascular volume and blood pressure in CKD. Calcitriol modulates the RAAS system by suppressing renin gene and angiotensin-converting enzyme expression [14,15]. Blocking RAAS with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers controls arterial hypertension, reduces proteinuria, and prevents or reverses endothelial dysfunction and atherosclerosis in patients with CKD [16].…”

mentioning

confidence: 99%

Editorial over the Many Faces of Vitamin D in Chronic Kidney Disease: from Mineral to Immune-Inflammatory Modulator

Honoré

Spapen

2017

Inflammation

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Vitamin D (vit D), whether produced in the skin or absorbed from the diet, is first metabolized in the liver to generate 25-hydroxyvitamin D (25OHD) and then hydroxylated in the proximal renal tubule to 1,25-dihydroxyvitamin D (1,25(OH) 2 D). 1,25(OH) 2 D (calcitriol) is the major biologically active metabolite and serves a paracrine/autocrine function. 1,25(OH) 2 D forms a complex with the vit D nuclear receptor which binds to vit D response elements in the deoxyribonucleic acid (DNA). Thousands of these binding sites regulate hundreds of genes creating a multitude of genomic effects that modulate cell activation, proliferation, and differentiation within the immune-inflammatory system [1]. This underpins the biological rationale for a potential beneficial partnership of vit D in a variety of immune-inflammatory conditions that largely transcends its undisputed regulatory role in calcium/phosphate homeostasis and bone mineralization [2,3].Chronic kidney disease (CKD) is an intricate pathology characterized by a state of accelerated cardiovascular deterioration. Persistent inflammation has been recognized as an important component of CKD and may in part account for cardiovascular and all-cause mortality [4]. Low levels of both 25OHD and 1,25(OH) 2 D are observed in patients with CKD and are associated with higher mortality and faster progression of kidney disease [5]. In a recent issue of Inflammation, Zhao et al. showed that calcitriol significantly reduced tubulo-interstitial inflammation in a rodent renal injury model [6]. The authors linked this renoprotective effect to calcitriol-induced upregulation of zinc finger protein A20, a de-ubiquitinating enzyme which causes disruption of nuclear factor kappa B (NF-κB) dependent intracellular chemo-and cytokine production and suppresses apoptotic pathways [7].Whether this novel compelling insight into the cellular mechanism of action of vit D may change the current or future therapeutic approach of CKD is uncertain. Factors contributing to the progression of CKD are indeed not limited to perturbed mineral metabolism, chronic inflammation, and oxidative stress but also include proteinenergy wasting, pre-existing heart failure, arterial hypertension, iron deficiency, and dialysis-related injury [8]. Patients with CKD often present a "leaky gut" and/or profound alterations in gut microbial flora. Increased gut wall permeability promotes translocation of bacteria and endotoxin which continuously fuels an inflammatory state. Changes in the intestinal microbiome are highly determined by intraluminal influx of urea, dietary constituents, and occasional antimicrobial therapy [8,9]. Of note is that both intestinal leakage and microbial environment show large interpatient variability and cannot be quantified. In addition, accumulation of protein-bound toxins (e.g., pcresyl sulfate and indoxyl sulfate) [10] and altered mucosal defense mechanisms may also contribute to cardiovascular events and sustain inflammation.Despite robust in vitro arguments to support the renoprotectiv...

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Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D₃ kinetics for extrapolation from mouse to man: Commentary

Noh

Yang

Sekhon

et al. 2020

Biopharm & Drug Disp

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Calcitriol or 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] is the active ligand of the vitamin D receptor (VDR) that plays a vital role in health and disease. Vitamin D is converted to the relatively inactive metabolite, 25-hydroxyvitamin D 3 [25(OH)D 3 ], by CYP27A1 and CYP2R1 in the liver, then to 1,25(OH) 2 D 3 by a specific, mitochondrial enzyme, CYP27B1 (1α-hydroxylase) that is present primarily in the kidney. The degradation of both metabolites is mostly carried out by the more ubiquitous mitochondrial enzyme, CYP24A1. Despite the fact that calcitriol inhibits its formation and degradation, allometric scaling revealed strong interspecies correlation of the net calcitriol clearance (CL estimated from dose/AUC ∞ ), production rate (PR), and basal, plasma calcitriol concentration with body weight (BW). PBPK-PD (physiologically based pharmacokinetic-pharmacodynamic) modeling confirmed the dynamic interactions between calcitriol and Cyp27b1/Cyp24a1 on the decrease in the PR and increase in CL in mice. Close scrutiny of the literature revealed that basal levels of calcitriol had not been taken into consideration for estimating the correct AUC ∞ and CL after exogenous calcitriol dosing in both animals and humans, leading to an overestimation of AUC ∞ and underestimation of the plasma CL. In humans, CL was decreased in chronic kidney disease but increased in cancer. Collectively, careful pharmacokinetic data analysis and improved definition are achieved with PBPK-PD modeling, which embellishes the complexity of dose, enzyme regulation, and disease conditions. Allometric scaling and PBPK-PD modeling were applied successfully to extend the PBPK model to predict calcitriol kinetics in cancer patients. K E Y W O R D Sallometric scaling, calcitriol or 1,25(OH) 2 D 3 , CYP24A1, CYP27B1, pharmacokinetics

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1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter

Cited by 435 publications

References 47 publications

Vitamin D deficiency and myocardial diseases

Vitamin D deficiency and myocardial diseases

Editorial over the Many Faces of Vitamin D in Chronic Kidney Disease: from Mineral to Immune-Inflammatory Modulator

Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D₃ kinetics for extrapolation from mouse to man: Commentary

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1,25-Dihydroxyvitamin D3 Suppresses Renin Gene Transcription by Blocking the Activity of the Cyclic AMP Response Element in the Renin Gene Promoter

Cited by 435 publications

References 47 publications

Vitamin D deficiency and myocardial diseases

Vitamin D deficiency and myocardial diseases

Editorial over the Many Faces of Vitamin D in Chronic Kidney Disease: from Mineral to Immune-Inflammatory Modulator

Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D3 kinetics for extrapolation from mouse to man: Commentary

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Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D₃ kinetics for extrapolation from mouse to man: Commentary