Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increasing prevalence of chronic kidney disease (CKD) in the United States demands a closer evaluation of and attention to associated morbidities, and, particularly, the rising mortality related to cardiovascular disease in all age groups. Patients with CKD demonstrate an increased risk of coronary artery disease due to calcium deposition and subsequent arterial stiffening, in addition to left ventricular dysfunction with associated heart failure and arrhythmias. While clearly impacted by the traditional risk factors for development of cardiovascular disease (CVD), patients with CKD are also affected by non-traditional risk factors, including calcium overloading related to aggressive management of secondary hyperparathyroidism. Recent data have shown that a substantial number of patients with CKD are deficient in vitamin D on a nutritional basis, in addition to the known decrease in the kidney-produced active metabolite during progressive CKD. Historically, vitamin D has been described as an endocrine hormone that regulates blood calcium and parathyroid hormone levels. It has become increasingly clear, through the recognition of a vitamin D receptor in most tissues, that vitamin D possesses functions well beyond calcium homeostasis, such that a deficiency may contribute to the development of CVD. In this brief review, the role of vitamin D activation through its vitamin D receptor will serve as an introduction to the magnitude of the nutritional deficits in children, adults, and those with CKD. As therapeutic entities in the management of renal osteodystrophy, vitamin D analogues play an important role in cardiovascular health that continues to evolve. Preliminary studies indicate that vitamin D therapy for control of secondary hyperparathyroidism may confer cardioprotection and reduce mortality. Attention to care of osteodystrophy in CKD must take into account heart health as well.
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PMID:Renal osteodystrophy in children: a systemic disease associated with cardiovascular manifestations. 1662 9

1alpha,25-Dihydroxyvitamin D(3) [1,25D] deficiency and vitamin D receptor [VDR] genotypes are risk factors for several diseases and disorders including heart diseases. Extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases [MMPs] contributes to progressive left ventricular remodeling, dilation, and heart failure. In the present study, we used high-density oligonucleotide microarray to examine gene expression profile in wild type [WT] and vitamin D receptor knockout mice (VDR KO) which was further validated by RT-PCR. Microarray analysis revealed tissue inhibitors of metalloproteinases [TIMP-1 and TIMP-3] were significantly under expressed in VDR KO mice as compared to WT mice which was further validated by RT-PCR. Zymography and RT-PCR showed that MMP-2 and MMP-9 were up regulated in VDR KO mice. In addition, cross-sectional diameter and longitudinal width of the VDR KO heart myofibrils showed highly significant cellular hypertrophy. Trichrome staining showed marked increase in fibrotic lesions in the VDR KO mice. Heart weight to body weight ratio showed approximately 41% increase in VDR KO mice when compared to WT mice. This data supports a role for 1,25D in heart ECM metabolism and suggests that MMPs and TIMPs expression may be modulated by vitamin D.
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PMID:Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. 1727 88

Vitamin D is an important prohormone for optimal intestinal calcium absorption for mineralization of bone. Because the vitamin D receptor is present in multiple tissues, there has been interest in evaluating other potential functions of vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional studies have reported that vitamin D deficiency is associated with increased risk of CVD, including hypertension, heart failure, and ischemic heart disease. Initial prospective studies have also demonstrated that vitamin D deficiency increases the risk of developing incident hypertension or sudden cardiac death in individuals with preexisting CVD. Very few prospective clinical studies have been conducted to examine the effect of vitamin D supplementation on cardiovascular outcomes. The mechanism for how vitamin D may improve CVD outcomes remains obscure; however, potential hypotheses include the downregulation of the renin-angiotensin-aldosterone system, direct effects on the heart, and vasculature or improvement of glycemic control. This review will examine the epidemiologic and clinical evidence for vitamin D deficiency as a cardiovascular risk factor and explore potential mechanisms for the cardioprotective effect of vitamin D.
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PMID:Vitamin D deficiency and risk for cardiovascular disease. 1959 2

Exposure of the skin to sunlight is now considered the most important source of vitamin D in Western countries. It is presumed to contribute approximately two thirds of the total requirement, leaving the remaining one third to the few foods naturally rich in this vitamin. In the skin, vitamin D is synthesized as a cholesterol chain which undergoes structural modifications following exposure to UVB rays. Once produced in the skin or absorbed in the gut as cholecalciferol, vitamin D enters the blood to be transported by a specific vitamin D binding protein, which is synthesized in the liver and has a powerful buffering capacity. The transport system carries the metabolites to the sites of further activation (25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney), ultimately resulting in the production of calcitriol. This last compound, now regarded as a hormone, circulates freely in minimal amounts and, compared with the other metabolites, shows the highest affinity for the vitamin D receptor (VDR). The mechanism of VDR activation is rather complex, resulting in either stimulation or inhibition of protein synthesis. Importantly, besides its presence in parathyroid, bone, kidney and intestine, this receptor has been demonstrated in several tissues, where its stimulation results in a reduced proliferation rate and increased differentiation. Accordingly, vitamin D is now regarded as a complex hormonal system, involved not only in the regulation of divalent ions and bone, but also in the proliferation and differentiation of numerous cell types with potential involvement in several diseases like cancer, immune diseases, diabetes, hypertension and heart failure.
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PMID:[Understanding the different functions of vitamin D]. 1964 19

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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PMID:Vitamin D deficiency and myocardial diseases. 2035 23

Vitamin D has recently been suggested as an important mediator of blood pressure and cardiovascular disease, including heart failure. In patient with heart failure, low vitamin D levels are associated with adverse outcome and correlate with established clinical correlates and biomarkers. Many precursor states of heart failure, such as hypertension, atherosclerosis, and diabetes are more prevalent in subjects with low vitamin D levels. Recent experimental data have provided clues how vitamin D might exert cardioprotective effects. The steroid hormone vitamin D regulates gene expression of many genes that play a prominent role in the progression of heart failure, such as cytokines and hormones. Specifically, vitamin D is a negative regulator of the hormone renin, the pivotal hormone of the renin-angiotensin system. Mechanistic insights were gained by studying mice deficient for the vitamin D receptor, which develop hypertension and adverse cardiac remodeling mediated via the renin-angiotensin system. Furthermore, vitamin D receptor is expressed in the heart and regulated under pro-hypertrophic stimuli and vitamin D as receptor has been associated with the expression of other hypertrophic genes such as natriuretic peptides. So, epidemiological data and mechanistic studies have provided strong support for a potentially cardioprotective effect of vitamin D. It remains unclear if vitamin D supplementation is beneficial in preventing heart failure or if it could be a therapeutic addendum in the treatment of heart failure. This review summarizes current knowledge on vitamin D and its biology in heart failure.
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PMID:Vitamin D biology in heart failure: molecular mechanisms and systematic review. 2079 39

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.
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PMID:Should vitamin D status be assessed in patients with congestive heart failure? 2039 85

An estimated 1 billion people worldwide have deficient or insufficient levels of vitamin D. Even more alarming is the association of vitamin D deficiency with many types of diseases, particularly heart failure (HF). Hypovitaminosis D has been observed to be highly prevalent in the HF community with rates varying from approximately 80% to 95%. Higher rates of deficiency have been linked to winter months, in patients with protracted decompensated HF, darker skin pigmentation, and higher New York Heart Association (NYHA) classes. In fact, some data suggest vitamin D deficiency may even be an independent predictor of mortality in patients with HF. Traditionally obtained through UV exposure and activated in the liver and then the kidneys, vitamin D is classified as a vitamin but functions as a steroid hormone. The hormone acts through the vitamin D receptor (VDR), which is expressed in vascular smooth muscle cells, renal juxtaglomerular cells, and most interestingly, cardiac myocytes. Studies have shown that the association between vitamin D deficiency and HF often manifests in the structural components of cardiac myocytes and/or through alterations of the neurohormonal cascade. In addition, vitamin D may also act rapidly through intracellular nongenomic receptors that alter cardiac contractility. Unfortunately, prospective vitamin D supplementation trials show mixed results. In rat models, successful correction of deficiency was associated with reductions in ventricular hypertrophy. In humans, however, echocardiographic dimensions did not change significantly. These results bring into questions whether vitamin D is a risk factor for HF, a marker of HF disease severity, or has a true pathologic role. This article provides a thorough review of vitamin D deficiency etiology, prevalence, and possible pathophysiologic role in HF. Furthermore, we carefully review prospective trials on vitamin D therapy in HF. We believe more trials on vitamin D therapy in HF need to be conducted before any conclusions can be drawn.
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PMID:Is vitamin D deficiency associated with heart failure? A review of current evidence. 2130 56

The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure-associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1-7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways.
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PMID:New roles for renin and prorenin in heart failure and cardiorenal crosstalk. 2169 49

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.
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PMID:Vitamin D receptor activation and prevention of arterial ageing. 2319 45


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