vitamin-d-2 and Heart-Failure

The ubiquitous distribution of vitamin D receptors in the human body is responsible for the pleiotropic effects of vitamin D-receptor activation. We discuss the possible beneficial effects of a selective activator of vitamin D receptor, paricalcitol, on the cardiovascular system in chronic heart failure patients and chronic kidney patients, in light of new trials. Paricalcitol should provide additional clinical benefits over the standard treatment for chronic kidney and heart failure, especially in cases of cardiorenal syndrome.

Topics: Aging; Animals; Bone Density Conservation Agents; Cardio-Renal Syndrome; Cardiovascular System; Chronic Disease; Ergocalciferols; Heart Failure; Humans; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Renal Insufficiency, Chronic

Despite advanced medical and device-based therapies, congestive heart failure (CHF) remains a major medical problem, associated with significant morbidity and mortality. Vitamin D deficiency is prevalent in CHF and is associated with poor outcomes. In this manuscript we review the evidence linking vitamin D deficiency and CHF and discuss potential mechanisms involved, as well the clinical data on vitamin D supplementation in CHF patients.. A clear relationship has been established between Vitamin D deficiency and increased mortality and morbidity in CHF. However, the mechanism involved is not clearly understood. Recent clinical and experimental evidence have identified the renin-angiotensin-aldosterone system and inflammatory cytokines as likely mediators that can lead to poor clinical outcomes via the cardiorenal syndrome. Clinical data on vitamin D supplementation also remain unestablished, with potential clinical benefits recently reported in patients with vitamin D deficiency. Nonetheless, large-scale randomized clinical trials are lacking.. Vitamin D is an emerging agent with tremendous potential and may represent a novel target for therapy in CHF. Further studies are needed to identify the mechanism(s) involved in the pathophysiology as well as to adequately examine the role of Vitamin D measurement and supplementation in patients with CHF.

Topics: Chronic Disease; Disease Progression; Ergocalciferols; Heart Failure; Humans; Vitamin D; Vitamin D Deficiency; Vitamins

The synthetic vitamin D3 analogue paricalcitol acts as a selective activator of the vitamin D receptor (VDR). While there is evidence for cardioprotective effects of paricalcitol associated with the VDR pathway, less information is available about the structural and functional cardiac effects of paricalcitol on established heart failure (HF) and particularly its effects on associated electrophysiological or Ca. We used a murine model of transverse aortic constriction (TAC) to study the effect of paricalcitol on established HF. Treatment was initiated 4 weeks after surgery over five consecutive weeks, and mice were sacrificed 9 weeks after surgery. Cardiac MRI (CMRI) was performed 4 and 9 weeks after surgery. Hearts were used for biochemical and histological studies and to isolate ventricular myocytes for electrophysiological and calcium imaging studies.. CMRI analysis revealed that, compared with vehicle, paricalcitol treatment prevented the progression of ventricular dilation and hypertrophy after TAC and halted the corresponding decline in ejection fraction. These beneficial effects were related to the attenuation of intracellular Ca. The results suggest that paricalcitol treatment in established HF hampers disease progression and improves adverse electrophysiological and Ca

Topics: Animals; Cardiomegaly; Disease Models, Animal; Ergocalciferols; Heart Failure; Mice; Myocytes, Cardiac

BACKGROUND Fabry disease is a rare and progressive X-linked inherited disorder of glycosphingolipid metabolism that is due to deficient or absent lysosomal a-galactosidase A activity. Among its other associated signs and symptoms, patients present with renal failure and proteinuria, which are markers of disease progression. Renin-angiotensin-aldosterone system (RAAS) blockers can slow the progression of chronic renal failure and proteinuria. In fact, some studies have shown the beneficial effects of paricalcitol on proteinuria. CASE REPORT We present a case of a female patient with the classic variant of Fabry disease. She was treated with a high dose of paricalcitol as an antiproteinuric agent due to unsatisfactory double-RAAS blockage, which resulted in transient worsening of cardiac and renal function. CONCLUSIONS Despite the positive effects of paricalcitol as an antiproteinuric agent, as previously shown by some authors, our case highlights the possible serious adverse effects associated with the use of high doses of this drug.

Topics: Adult; Bone Density Conservation Agents; Clinical Deterioration; Dose-Response Relationship, Drug; Ergocalciferols; Fabry Disease; Female; Heart Failure; Humans; Kidney Failure, Chronic; Proteinuria

Accumulating evidence suggests that vitamin D deficiency plays a crucial role in heart failure. However, whether vitamin D signaling itself plays an important role in cardioprotection is poorly understood. In this study, we examined the mechanism of modulating vitamin D signaling on progression to heart failure after myocardial infarction (MI) in mice. Vitamin D signaling was activated by administration of paricalcitol (PC), an activated vitamin D analog. Wild-type (WT) mice underwent sham or MI surgery and then were treated with either vehicle or PC. Compared with vehicle group, PC attenuated development of heart failure after MI associated with decreases in biomarkers, apoptosis, inflammation, and fibrosis. There was also improvement of cardiac function with PC treatment after MI. Furthermore, vitamin D receptor (VDR) mRNA and protein levels were restored by PC treatment. Next, to explore whether defective vitamin D signaling exhibited deleterious responses after MI, WT and VDR knockout (KO) mice underwent sham or MI surgery and were analyzed 4 wk after MI. VDR KO mice displayed a significant decline in survival rate and cardiac function compared with WT mice after MI. VDR KO mice also demonstrated a significant increase in heart failure biomarkers, apoptosis, inflammation, and fibrosis. Vitamin D signaling promotes cardioprotection after MI through anti-inflammatory, antifibrotic and antiapoptotic mechanisms.

Topics: Animals; Apoptosis; Biomarkers; Cells, Cultured; Chemokine CCL2; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type III; Disease Models, Animal; Ergocalciferols; Fibrosis; Heart Failure; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Recovery of Function; RNA, Messenger; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Function, Left; Vitamins

A dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to-marked severity (<20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established.. Herein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO₃ (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, <35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored.. Reduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05).. Thus, the 14-week course of supplemental vitamin D and CaCO₃ led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.

Topics: Black or African American; Calcium Carbonate; Calcium, Dietary; Cardiomyopathy, Dilated; Cholecalciferol; Dietary Supplements; Dinoprost; Ergocalciferols; Female; Heart Failure; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Parathyroid Hormone; Stroke Volume; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure.. When male Dahl salt-sensitive rats were fed a high salt (HS) diet, all rats developed cardiac hypertrophy after 5 weeks. Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analogue, at 200 ng, IP 3x/week), enalapril (EP, 90 μg/day), and PC + EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC + EP groups, but not the V and EP only groups, showed significant prevention of progression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC + EP therapy. The expression of PKCα, which is regulated by Ca(2+)and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC + EP effectively decreased PKCα activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment.. PC treatment resulted in both the prevention of progression of pre-existing cardiac hypertrophy and the development of heart failure, compared with improvement in progression to heart failure by EP alone. These beneficial findings in heart were associated with inhibition of PKCα activation and reversal of gene alterations.

Topics: Animals; Calcium; Cardiomegaly; Disease Progression; Ergocalciferols; Gene Expression Profiling; Heart Failure; Hemodynamics; Male; Protein Kinase C-alpha; Rats; Rats, Sprague-Dawley

Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an antihypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats.. Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally at 150 ng, 3 times per week (Monday, Wednesday, Friday) for 6 weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency.. Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Ergocalciferols; Heart Failure; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred Dahl; RNA, Messenger; Signal Transduction; Ultrasonography; Vitamins

Topics: Adult; Biological Transport; Bone and Bones; Calcium; Cell Membrane Permeability; Diabetic Retinopathy; Ergocalciferols; Female; Heart Failure; Humans; Hypercalcemia; Peritoneal Dialysis; Peritoneum; Phosphorus; Solutions; Uremia