Role of Vitamin D Receptor Activators in Cardio-Renal Syndromes

Cozzolino, Mario; Bruschetta, Elena; Stucchi, Andrea; Ronco, Claudio; Cusi, Daniele

doi:10.1016/j.semnephrol.2011.11.009

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…Among the VDR activators, selective activators such as Paricalcitol play a major role in controlling mineral metabolism. These selective molecules act more efficiently on parathyroid glands rather than on intestine and bone; this leads both to a lower serum calcium and phosphorus increases and to an improvement of hyperplasia of the parathyroid gland and secondary hyperparathyroidism [15]. For these reasons, selective VDR activators could provide a vitamin D-like protective efficacy without the hypercalcemic and hypophosphatemic collateral effects, thus representing a potential therapeutic tool against the cardio-renal syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Paricalcitol (19-nor-1,25-dihydroxyvitamin D 2 ) is a vitamin D 3 analog, acting as a selective VDR activator; for this reason it might provide a vitamin D 3 -like protective efficacy without the hypercalcemic and hypophosphatemic side effects of vitamin D 3 , thus representing a potentially useful tool against the cardio-renal syndrome [12,15]. In particular, to better evaluate the modifications of the intracellular energy status as well as the modifications in signal transduction, in this study we compared the effects of vitamin D 3 , to those of paricalcitol in a myoblastic cell line H9c2, not completely differentiated showing electrophysiological and biochemical properties of cardiac muscle tissue [16].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

et al. 2013

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Cardiovascular diseases are more prevalent in patients with chronic kidney disease than in the general population and they are considered the leading cause of death in patients with end-stage renal disease. The discovery that vitamin D3 plays a considerable role in cardiovascular protection has led, in recent years, to an increase in the administration of therapies based on the use of this molecule; nevertheless, several studies warned that an excess of vitamin D3 may increase the risk of hypercalcemia and vascular calcifications. In this study we evaluated the effects of vitamin D3, and of its selective analog paricalcitol, on immature cardiomyocytes. Results show that vitamin D3 induces cAMP-mediated cell proliferation and significant intracellular calcification. Paricalcitol, however, induces cell differentiation, morphological modifications in cell shape and size, and no intracellular calcification. Furthermore, vitamin D3 and paricalcitol differently affect cardiomyoblasts responses to acetylcholine treatment. In conclusion, our results demonstrate that the effects of vitamin D3 and paricalcitol on cardiomyoblasts are different and, if these in vitro observations could be extrapolated in vivo, they suggest that paricalcitol has the potential for cardiovascular protection without the risk of inducing intracellular calcification.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

et al. 2013

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“…Because vitamin D is activated to 1,25(OH) 2 D in the kidney, uremia changes homeostatic mechanisms, where vitamin D signaling plays a critical role, with vitamin D agonists offering therapeutic benefits. 129 In a mouse chronic kidney disease model, therapeutic dosage (sufficient to correct secondary hyperparathyroidism) of the VDR activator, paricalcitol, reduced aortic osteoblastic gene expression and calcification, but high dosage (400 ng/kg) caused a significant increase in calcification. 130 This highlights the dose-dependent role of vitamin D in vascular calcification, and presumably cardiovascular health.…”

Section: Vascular Calcificationmentioning

confidence: 99%

Vitamin D and Cardiovascular Disease

Norman¹,

Powell

2014

Circulation Research

450

353

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Vitamin D (nutritional term for compounds with biological activity of 1α,25-dihydroxyvitamin D; also used to indicate summation of Vitamin D 2 and D 3 ) is a fat-soluble vitamin that functions as a steroid hormone. It plays a crucial role in mineral homeostasis and skeletal health and its deficiency classically leads to rickets in children and osteomalacia in adults. 1 Its primary action on the skeletal system is to regulate calcium and phosphorus metabolism by influencing intestinal absorption, bone resorption, and renal retention (Figure 1). Vitamin D metabolites also play an integral physiological role in nonskeletal tissues and have been implicated in a wide range of chronic pathology, including skin and autoimmune disease, cancer, diabetes mellitus, hypertension, and cardiovascular disease (CVD).2 Interest in the role of vitamin D in CVD arose from evidence of adverse cardiovascular effects of vitamin D deficiency in animal models, 3 and epidemiological studies reporting the increase in cardiovascular events in winter and at increasing distance from the equator. Various extrarenal tissues, including many cell types involved in CVD, also express CYP27B1 and are therefore able to produce 1,25(OH) 2 D. This local production and breakdown is not subject to the same feedback controls as renal production. Vitamin D Deficiency and ExcessThere is controversy about the definition of vitamin D deficiency (or hypovitaminosis D), the optimum serum level of 25(OH)D, and the dietary requirements of vitamin D.

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“…Although the administration of vitamin D has positive effects through inhibition of PTH secretion, it also results in increased serum phosphate levels, with opposing effects (see next paragraph for details). When modulating vitamin D status, one should consider the use of vitamin D analogues, such as paricalcitol, which inhibit PTH synthesis, without substantially inducing hyperphosphatemia, providing promising therapies for restoration of vitamin D levels (Cozzolino et al, 2012).…”

Section: Consequences Of Chronic Kidney Disease On Mineral Metabolismmentioning

confidence: 99%

Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction: A Focus on Microcirculatory Factors and Therapeutic Targets

et al. 2019

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Heart failure (HF) and chronic kidney disease (CKD) co-exist, and it is estimated that about 50% of HF patients suffer from CKD. Although studies have been performed on the association between CKD and HF with reduced ejection fraction (HFrEF), less is known about the link between CKD and heart failure with preserved ejection fraction (HFpEF). Approximately, 50% of all patients with HF suffer from HFpEF, and this percentage is projected to rise in the coming years. Therapies for HFrEF are long established and considered quite successful. In contrast, clinical trials for treatment of HFpEF have all shown negative or disputable results. This is likely due to the multifactorial character and the lack of pathophysiological knowledge of HFpEF. The typical co-existence of HFpEF and CKD is partially due to common underlying comorbidities, such as hypertension, dyslipidemia and diabetes. Macrovascular changes accompanying CKD, such as hypertension and arterial stiffening, have been described to contribute to HFpEF development. Furthermore, several renal factors have a direct impact on the heart and/or coronary microvasculature and may underlie the association between CKD and HFpEF. These factors include: (1) activation of the renin-angiotensin-aldosterone system, (2) anemia, (3) hypercalcemia, hyperphosphatemia and increased levels of FGF-23, and (4) uremic toxins. This review critically discusses the above factors, focusing on their potential contribution to coronary dysfunction, left ventricular stiffening, and delayed left ventricular relaxation. We further summarize the directions of novel treatment options for HFpEF based on the contribution of these renal drivers.

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Role of Vitamin D Receptor Activators in Cardio-Renal Syndromes

Cited by 8 publications

References 49 publications

Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

Effects of Vitamin D3 and Paricalcitol on Immature Cardiomyocytes: A Novel Role for Vitamin D Analogs in the Prevention of Cardiovascular Diseases

Vitamin D and Cardiovascular Disease

Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction: A Focus on Microcirculatory Factors and Therapeutic Targets

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