Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1 alpha-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and extracellular Ca(2+) act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)(2)D(3)-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.
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PMID:Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology. 1972 93

Vitamin D insufficiency/deficiency has been worldwide reported in all age groups in recent years. It has been considered a Public Health matter since decreased levels of vitamin D has been related to several chronic diseases, as type 2 diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and insulin secretion has been observed during vitamin D deficiency, both in animals and humans resulting in T2DM. The supposed mechanism underlying these findings is presence of vitamin D receptor in several tissues and cells, including pancreatic beta-cells, adipocyte and muscle cells. In obese individuals, the impaired vitamin D endocrine system, characterized by high levels of PTH and 1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of 25(OH)D and also contribute to a higher intracellular calcium, which in turn secrete less insulin and deteriorate insulin sensitivity. In hypertension, vitamin D could act on renin-angiotensin system and also in vascular function. Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and inhibit vascular smooth muscle cell proliferation. However, prospective and intervention human studies that clearly demonstrates the benefits of vitamin D status adequacy in the prevention and treatment of endocrine metabolic diseases are lacking. Further research still necessary to assure the maximum benefit of vitamin D in such situations.
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PMID:[Vitamin D and endocrine diseases]. 1976 53

Deficiencies in vitamin D and vitamin D receptor (VDR) activation adversely affect cardiovascular health in the general population and in people at high risk of cardiovascular disease, as well as contributing to secondary hyperparathyroidism in patients with chronic kidney disease (CKD). Furthermore, epidemiological and observational data indicate that there is a close interrelationship between progressive renal dysfunction in CKD, cardiovascular disease, and mortality. The causes of death in patients even with only moderate kidney dysfunction are commonly associated with cardiovascular events. Modulation of vitamin D levels results in correlative regulatory effects on mineral homeostasis, hypertension, vascular disease, and calcification, as well as a number of other endpoints in cardiac and renal disease. The use of VDR activators to treat these and other parameters outside of cardiovascular and renal disease not only results in enhanced patient health but significantly lowers the risk of mortality in CKD and non-CKD patients with low systemic activity of vitamin D. The cardiovascular and renal systems continue to demonstrate their interrelated effects on each other, particularly when vitamin D and VDR signaling are considered.
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PMID:[Prevention and treatment of secondary hyperparathyroidism in non-dialyzed patients with stage 3-5 chronic kidney diease]. 1994 Dec 76

The calcineurin inhibitors-cyclosporine and tacrolimus-are the mainstay of immunosuppressive therapy in solid organ transplantation. These drugs produce severe adverse drug effects (ADEs) such as nephrotoxicity, posttransplantation diabetes mellitus, and hypertension. Accumulated evidence suggests that the development of type 2 diabetes, hypertension, and renal failure may be associated with specific DNA genotypes. In this review, the genes involved with the development of these disease processes are compared with those implicated in calcineurin inhibitor-induced ADEs. The renin-angiotensin system genes, cytokine-encoding genes, and plasminogen activator inhibitor type 1 genes have been implicated in calcineurin inhibitor-induced nephrotoxicity, as well as in development of renal failure. A number of genes are implicated in contributing to diabetes, and these include the vitamin D receptor gene, VDR; hepatocyte nuclear factor genes, HNF; transcription factor 7-like 2 gene, TCF7L2; angiotensin-converting enzyme gene, ACE; cytokines; peroxisome proliferator-activated receptor gamma gene, PPARG; and others. Studies have suggested that the VDR, PPARG, HNF1A, and adenosine 5'-triphosphate-binding cassette ABCC8 (which encodes the sulfonylurea receptor) genes are associated with calcineurin inhibitor-induced diabetes. The genes encoding for the angiotensin-converting enzyme, endothelial constitutive nitric oxide synthase, and cytochrome P450 3A isoenzyme have been involved in the development of hypertension and in calcineurin inhibitor-induced hypertension. The genetic study of disease states can be the stepping stones for thoroughly understanding the genetic basis of ADEs. Gene polymorphisms are implicated in the development of diseases and corresponding disease-like ADEs. The disease-associated genes provide candidate genes for exploring ADEs and may provide genomic biomarkers for assessing the risk for developing severe calcineurin inhibitor-related ADEs as well as for developing preventive strategies.
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PMID:Understanding the genetic basis for adverse drug effects: the calcineurin inhibitors. 2009 93

At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.
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PMID:New therapies: calcimimetics, phosphate binders and vitamin D receptor activators. 2015 Nov 57

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Traditional causes such as diabetes, smoking, aging and hypertension do not fully explain the high rate of morbidity from cardiovascular disease seen in these patients. The renin-angiotensin-aldosterone system (RAAS) regulates extracellular volume homeostasis, which contributes to blood pressure stability. Overactivity of this system is involved in the pathophysiology of cardio-renal disease. New evidence suggests that vitamin D receptor activators (VDRAs) have a suppressive effect on the RAAS; however, VDRAs also have anti-inflammatory and anti-fibrotic effects. We have demonstrated that paricalcitol, a VDRA, ameliorates left ventricular hypertrophy (LVH) in uremic rats by up-regulating the VDR, decreasing myocardial PCNA and also decreasing myocardial oxidative stress. Thus, paricalcitol can suppress the progression of LVH, myocardial and perivascular fibrosis and myocardial arterial vessel thickness presumably by up-regulating the VDR. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD. Prospective randomized studies in CKD patients are necessary to confirm these results.
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PMID:Myocardial effects of VDR activators in renal failure. 2023 14

The hypothesis that vitamin D is inversely associated with multiple health outcomes has been studied in the Harvard cohorts, including the Nurses' Health Study I (n=121,700 female nurses aged 37-64 at baseline in 1984), Nurses' Health Study II (n=116,671 female nurses aged 27-44 years at baseline in 1991), Health Professionals Follow-up Study (n=51,529 male health professionals aged 40-75 years at baseline in 1986), and Physicians' Health Study (n=22 071 male physicians aged 40-84 years at baseline in 1982). These studies assessed vitamin D through circulating 25-hydroxyvitamin D, dietary and supplemental intake, predicted 25-hydroxyvitamin D, and vitamin D receptor polymorphisms. This review summarizes studies of vitamin D and various endpoints considered in these cohorts, including risk of cardiovascular disease, hypertension, elevated plasma C-peptide, various cancers, bone fractures, and multiple sclerosis. Based on the multiple observed benefits of vitamin D, this article postulates recommendations for vitamin D intake in the US population for reduced incidence of multiple health outcomes.
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PMID:Vitamin D and multiple health outcomes in the Harvard cohorts. 2048 9

Chronic kidney disease (CKD) has been recognized as a significant public health problem, with 20 million Americans, or 11% of the adult population, currently living with CKD. Life expectancy in patients with CKD is limited by the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a reduction in renal 1alpha-hydroxylase activity and thus in renal production of calcitriol at very early CKD stages. Recently, a potentially important role of vitamin D receptor activation (VDRa) in the survival of patients undergoing dialysis has been suggested. Beyond the effect on parathyroid hormone suppression, the pleiotropic effect of vitamin D has been associated with improvement of cardiovascular risk factors, including increased renin activity, hypertension, inflammation, insulin resistance, diabetes, and albuminuria. However, the current K/DOQI and KDIGO recommendations limit the administration of VDRa agents for treatment of hyperparathyroidism only. The role of vitamin D administration in the different CKD stages will be discussed in this review.
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PMID:Use of vitamin D in chronic kidney disease patients. 2050 58

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.
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PMID:The vitamin D system: a crosstalk between the heart and kidney. 2060 45

The role of vitamin D in multiple organ systems has come into sharp focus with recent advances in the understanding of its mechanisms of actions and specific effects of vitamin D preparations that serve as substrates and those that directly activate the vitamin D receptor. Major progress has been made in understanding the interplay between the vitamin D system and the FGF23/Klotho system for regulation of renal phosphate excretion. While recognizing the importance of treating secondary hyperparathyroidism in chronic kidney disease, the current interests have moved beyond this indication and are focusing on the role of vitamin D receptor and its activators in the basic pathophysiology of hypertension, cardiovascular disease, kidney disease, and overall patient outcomes.
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PMID:Introduction to the third annual rostand vitamin D symposium. 2061 60


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