Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D has many physiological functions. First it is a primary regulator of calcium homeostasis. Beyond that, vitamin D and its receptors (VDR) play important role in the immune system, cardiovascular system, reproductive system and insulin resistance. An important aspect of vitamin D pleiotropic effects is the interaction with components of the renin-angiotensin system (RAS). It was demonstrated that vitamin D-null mice have a sustained elevation of renin expression. The combination of both the AT1 blockers and the vitamin D analogues, leads to a marked amelioration of the molecular and clinical markers of diabetic nephropathy. This combination may protect the kidney through the effects on both the glomerular and the tubulointerstitial compartments. There are different studies that corroborate the renoprotective action of vitamin D in CKD. In fact the renoprotective mechanisms in humans remain to be assessed, but these are realized through reduction of proteinuria, high blood pressure, inflammation as well as hemodynamic effects. An important mechanism is the role of vitamin D as a potent negative endocrine regulator of renin expression. It was shown that low levels of vitamin D represent a novel risk factor for the progression of renal disease but it is not demonstrated yet that vitamin D can prolong the time to end-stage renal disease. This question remains to be answered in other future controlled clinical trials.
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PMID:Renoprotective effects of Vitamin D and renin-angiotensin system. 2439 10

Vitamin D deficiency (VDD) is prevalent among HIV-infected individuals. Vitamin D has been associated with renal and cardiovascular diseases because of its effects on oxidative stress, lipid metabolism and renin-angiotensin-aldosterone system (RAAS). Tenofovir disoproxil fumarate (TDF), a widely used component of antiretroviral regimens for HIV treatment, can induce renal injury. The aim of this study was to investigate the effects of VDD on TDF-induced nephrotoxicity. Wistar rats were divided into four groups: control, receiving a standard diet for 60 days; VDD, receiving a vitamin D-free diet for 60 days; TDF, receiving a standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days; and VDD+TDF receiving a vitamin D-free diet for 60 days with the addition of TDF for the last 30 days. TDF led to impaired renal function, hyperphosphaturia, hypophosphatemia, hypertension and increased renal vascular resistance due to downregulation of the sodium-phosphorus cotransporter and upregulation of angiotensin II and AT1 receptor. TDF also increased oxidative stress, as evidenced by higher TBARS and lower GSH levels, and induced dyslipidemia. Association of TDF and VDD aggravated renovascular effects and TDF-induced nephrotoxicity due to changes in the redox state and involvement of RAAS.
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PMID:Vitamin D deficiency aggravates nephrotoxicity, hypertension and dyslipidemia caused by tenofovir: role of oxidative stress and renin-angiotensin system. 2504 68

Hypertension is one of the major predisposing factors for neurodegenerative disease characterized with activated renin-angiotensin system (RAS) in both periphery and brain. Vitamin D (VitD) is recently recognized as a pleiotropic hormone with strong neuroprotective properties. While multiple lines of evidence suggest that VitD can act on RAS, the evidence concerning the crosstalk between VitD and RAS in the brain is limited. Therefore, this study aims to evaluate whether VitD can modulate brain RAS to trigger neuroprotective actions in the brain of spontaneously hypertensive rats (SHR). Our data showed that calcitriol treatment induced VDR expression and inhibited neural death in the prefrontal cortex of SHR. Sustained calcitriol administration also inhibited microglia M1 polarization, but enhanced M2 polarization, accompanied with decreased expression of proinflammatory cytokines. We then further explored the potential mechanisms and showed that SHR exhibited overactivated classical RAS with increased expression of angiotensin II (Ang II) receptor type 1 (AT1), angiotensin converting enzyme (ACE) and Ang II production, whereas the counteracting arm of traditional RAS, ACE2/Ang(1-7)/MasR, was impaired in the SHR brain. Calcitriol nonsignificantly suppressed AT1 and ACE but markedly reduced Ang II formation. Intriguingly, calcitriol exerted pronouncedly impact on ACE2/Ang(1-7)/MasR axis with enhanced expression of ACE2, MasR and Ang(1-7) generation. Meanwhile, calcitriol ameliorated the overactivation of NADPH-oxidase (Nox), the downstream of RAS, in SHR, and also mitigated oxidative stress. In microglial (BV2) cells, we further found that calcitriol induced ACE2 and MasR with no significant impact on ACE and AT1. In accordance, calcitriol also attenuated Ang II-induced Nox activation and ROS production, and shifted the microglia polarization from M1 to M2 phenotype. However, co-treatment with A779, a specific MasR antagonist, abrogated the antioxidant and neuroimmune modulating actions of VitD. These findings strongly indicate the involvement of ACE2/Ang(1-7)/MasR pathway in the neuroprotective mechanisms of VitD in the hypertensive brain.
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PMID:Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system. 3142 10

Vitamin D (Vit.D) is involved in cellular proliferation and differentiation and regulation of the renin gene, which are important aspects of nephrogenesis and quiescence of renal health in adulthood. This study evaluated the angiogenic mechanisms involved in long term renal disturbances induced by Vit.D deficiency persistent in adulthood in rats. First-generation male Hannover offspring from mothers fed either a control diet (control group, CG) or Vit.D-deficient diet (Vit.D- group) were evaluated. Systolic blood pressure (SBP) was measured monthly during the first 6 months after birth, and blood and urine samples were collected to evaluate renal function. Nitric oxide (NO), angiotensin II (ANGII), parathyroid hormone (PTH), calcium, and Vit.D were measured. The kidneys were then removed for morphometric, NO, immunohistochemical, and Western blot studies. We evaluated the expression of vascular growth factor (VEGF) and angiopoietins 1 and 2 and their receptors since this intrinsic renal axis is responsible for endothelial quiescence. Compared to CG, the Vit.D- group presented higher SBP, ANG II plasma levels, renin expression, and AT1 receptor expression levels. Capillary rarefaction was observed, as well as an imbalance between pro- and anti-angiogenic factors. Collectively, the present findings support the role of Vit.D for maintaining the integrity of renal microcirculation.
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PMID:Imbalance of Pro- and Anti-Angiogenic Factors Due to Maternal Vitamin D Deficiency Causes Renal Microvasculature Alterations Affecting the Adult Kidney Function. 3142 37