Role of hyperphosphatemia-mediated vascular calcification in cardiovascular outcomes and its management

Latif, Faisal; Khalid, M.; Khan, Fahad; Omar, Zainab; Ali, Fazal

doi:10.2459/jcm.0b013e32835ec53d

Cited by 4 publications

(3 citation statements)

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“…The high levels of phosphate directly affect VSMCs and induce calcification [Liu et al, 2014]. Recent studies indicate that hyperphosphatemia is the leading cause and direct stimulus of vascular calcification, contributing to the high mortality caused by cardiovascular diseases [Koizumi and Fukagawa, 2010;Latif et al, 2013]. Thus, finding a possible molecular target of VC in ESRD might help us find a novel treatment for the disease.…”

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confidence: 99%

Retracted: Activation of the Nrf2‐ARE Signaling Pathway Prevents Hyperphosphatemia‐Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells

Wang

Tian

et al. 2017

J of Cellular Biochemistry

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This study investigates the effect of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in vascular calcification (VC) via inducing Autophagy in renal vascular smooth muscle cells (VSMCs). VSMCs were assigned into six experimental groups: the normal control, high phosphorus, si-negative control (si-NC), Nrf2-siRNA, over-expressed Nrf2, and negative control (NC) groups. RT-PCR was applied to detect the mRNA expressions of the desired Nrf2-ARE signaling pathway-related genes (Nrf2, NQO-1, HO-1, γ-GCS). The protein products of these genes: apoptosis-related genes (LC3I and LC3II), osteogenic marker proetins (Runt-related transcription factor 2) Runx2 and BMP2 were all detected by Western blotting. Autophagosomes in VSMCs were observed under a transmission electron microscope. We discovered an increased calcium ion concentration and upregulated Runx2, BMP2, Nrf2, HO-1, γ-GCS, NQO-1, and LC3II/LC3I expressions in the high phosphorous, si-NC and Nrf2-siRNA, and NC groups, compared with the normal control group. Compared to the high phosphorus and si-NC groups, higher levels of Runx2 and BMP2 but decreased Nrf2, HO-1, γ-GCS, NQO-1, and LC3II/LC3I expressions were detected in the Nrf2-siRNA group. The high phosphorus, si-NC and over-expressed Nrf2 experimental groups all had increased Nrf2, NQO-1, HO-1, γ-GCS, and LC3II/LC3I expressions as well as high numbers of autophagosomes compared with the normal control group. Finally, we detected a lower amount of autophagosomes presence and Nrf2, NQO-1, HO-1 γ-GCS, and LC3II/LC3 protein expression of Nrf2-siRNA group than that of the high phosphorus and si-NC groups. Activation of Nrf2-ARE signaling pathway may prevent hyperphosphatemia-induced VC by inducing autophagy in VSMCs. J. Cell. Biochem. 118: 4708-4715, 2017. © 2017 Wiley Periodicals, Inc.

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confidence: 99%

Retracted: Activation of the Nrf2‐ARE Signaling Pathway Prevents Hyperphosphatemia‐Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells

Wang

Tian

et al. 2017

J of Cellular Biochemistry

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“…Hyperphosphataemia in CKD is known to contribute to progressive vascular calcification and increase cardiovascular complications (Latif et al , ). Non‐Ca‐containing phosphate binders have been shown to be associated with a beneficial effect on vascular calcification progression in both preclinical and clinical studies (Frazao and Adragao, ; Raggi et al , ; Iida et al , ; Phan et al , ).…”

Section: Discussionmentioning

confidence: 99%

Preclinical studies of VS‐505: a non‐absorbable highly effective phosphate binder

Wu-Wong

Chen

Wong

et al. 2016

British J Pharmacology

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BACKGROUND AND PURPOSEPhosphate imbalance is often present in chronic kidney disease (CKD), and it contributes to a higher cardiovascular mortality rate. A phosphate binder is typically part of a treatment strategy for controlling phosphate imbalance. However, safety concerns and low compliance are two well-recognized disadvantages of on-market phosphate binders. This report describes the preclinical studies of VS-505, a non-absorbable, calcium-and aluminum-free, plant-derived polymer currently being evaluated in haemodialysis patients in Australia. EXPERIMENTAL APPROACHNormal Sprague Dawley (SD) rats or uraemic SD rats induced by 5/6 nephrectomy fed a high-phosphate diet were treated with VS-505 or sevelamer (0.05-10% in food) for 5 and 28 days respectively. KEY RESULTSUrinary and serum phosphate levels were significantly elevated in untreated rats, and were decreased by VS-505 and sevelamer. VS-505 increased faecal phosphate levels in a dose-dependent manner. High-phosphate diet also caused an increase in serum FGF-23 and parathyroid hormone in nephrectomized (NX) rats, effects prevented by VS-505 or sevelamer. Significant aortic calcification was observed in NX rats treated with 5% sevelamer, whereas VS-505 at all doses tested did not show effects. VS-505 had no effects on small intestine histomorphology and intestinal sodium-dependent phosphate cotransporter gene expression. In vitro characterizations showed that VS-505 has a relatively high density and low expansion volume when exposed to simulated gastric fluid. CONCLUSIONS AND IMPLICATIONSVS-505 is a safe and effective phosphate binder and may offer the advantage of having a reduced pill burden and minimal GI side effects for CKD patients. Abbreviations

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“…High serum phosphorus directly triggers vascular injury, increases the mineral deposition in vascular smooth muscle cells in studies in vitro [1], and increases vascular calcification in individuals with or without chronic kidney disease [2], which indicates a high risk of cardiovascular diseases (CVDs) [3]. Serum calcium plays an important role in excitation-contraction coupling of the myocardium, and the influx of extracellular calcium largely initiates and determines the degree of myocardial contraction.…”

Section: Introductionmentioning

confidence: 99%

Manifestations of left ventricular dysfunction and arrhythmia in patients with chronic hypoparathyroidism and pseudohypoparathyroidism: a preliminary study

Wang¹,

Wang

et al. 2020

BMC Endocr Disord

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Background: Cardiac damage triggered by severe hypocalcemia is well known. However, the role of chronic hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP) in cardiac health is still unclear. We investigated the effect of chronic HP and PHP on cardiac structure and conductive function in patients compiling with treatment. Methods: The study included 18 patients with HP and eight with PHP aged 45.4 ± 15.4 and 22.1 ± 6.4 years, respectively with a previously regular follow-up. In addition, 26 age-and sex-matched healthy controls were included. General characteristics and biochemical indices were recorded. Cardiac function and structure were assessed by estimation of myocardial enzymes, B-type natriuretic peptide (BNP), and echocardiography. The 12-lead electrocardiogram and 24-h Holter electrocardiography were performed to evaluate the conductive function.

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Role of hyperphosphatemia-mediated vascular calcification in cardiovascular outcomes and its management

Cited by 4 publications

References 71 publications

Retracted: Activation of the Nrf2‐ARE Signaling Pathway Prevents Hyperphosphatemia‐Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells

Retracted: Activation of the Nrf2‐ARE Signaling Pathway Prevents Hyperphosphatemia‐Induced Vascular Calcification by Inducing Autophagy in Renal Vascular Smooth Muscle Cells

Preclinical studies of VS‐505: a non‐absorbable highly effective phosphate binder

Manifestations of left ventricular dysfunction and arrhythmia in patients with chronic hypoparathyroidism and pseudohypoparathyroidism: a preliminary study

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