Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification

Viegas, Carla S. B.; Santos, Lúcia; Macedo, Anjos L.; Matos, A. P. Alves de; Silva, Ana Paula; Neves, Pedro Leão; Staes, An; Gevaert, Kris; Morais, Rute; Vermeer, Cees; Schurgers, Leon J.; Simes, Dina C.

doi:10.1161/atvbaha.117.310578

Cited by 124 publications

(176 citation statements)

References 42 publications

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“…Protein-bound uremic toxin can further aggravate this active calcification process in endothelial and medial layers of the vessel [7]. New concepts indicated that calciprotein particles (CPPs) and matrix vesicles (MVs) participate in passive calcification, which can be triggered by hyperphosphatemia and protein-bound uremic toxin-related inflammatory reactions, and lead to calcification within the medial layer of vessel [8][9][10]. In addition to the medial layer, VC can also occur in the intimal layer of the vessel wall.…”

Section: Introductionmentioning

confidence: 99%

Sirtuin-1 and Its Relevance in Vascular Calcification

Liao

Hou

et al. 2020

IJMS

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Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of β-catenin that, following the facilitation of β-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.

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Section: Introductionmentioning

confidence: 99%

Sirtuin-1 and Its Relevance in Vascular Calcification

Liao

Hou

et al. 2020

IJMS

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“…Recientemente, diferentes estudios han descrito a las MV como promotoras de la CV [ 17,21,22 ], lo que demuestra que las MV juegan un nuevo papel en esta patología. Sin embargo, el escaso número de MV de células musculares lisas circulantes hace muy difícil su traslación clínica para ser utilizadas como biomarcador que identifique sujetos en riesgo de desarrollar calcificación vascular.…”

Section: Discussionunclassified

Indoxil sulfato induce senescencia y liberación de microvesículas en células endoteliales que promueven la calcificación vascular

Escobar¹,

Bodega²,

Carracedo³

et al. 2020

DIANAS

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“…Besides preventing the precipitation of Ca-P i (Figure 2), CPP can induce pro-inflammatory effects in VSMC in vitro [84], further linking inflammation and EVA in CKD. Furthermore, CPP differ between healthy subjects and patients with ESKD and can, therefore, promote widespread calcification in CKD [85].…”

Section: The Endocrine Phosphate-fgf-23-klotho Axis and Premature Agementioning

confidence: 99%

Inflammation and Premature Ageing in Chronic Kidney Disease

Ebert

Pawelzik

Witasp

et al. 2020

Toxins

134

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Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.

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Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification

Abstract: Uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD. We propose a major role for cGRP as inhibitory factor to prevent calcification at systemic and tissue levels.

Cited by 124 publications

References 42 publications

Sirtuin-1 and Its Relevance in Vascular Calcification

Sirtuin-1 and Its Relevance in Vascular Calcification

Indoxil sulfato induce senescencia y liberación de microvesículas en células endoteliales que promueven la calcificación vascular

Inflammation and Premature Ageing in Chronic Kidney Disease

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