Activation of the calcium-sensing receptor in human valvular interstitial cells promotes calcification

Issa, Hawraa; Hénaut, Lucie; Abdallah, Jeanne Bou; Boudot, Cédric; Lenglet, Gaëlle; Avondo, Carine; Ibrik, Aida; Caus, Thierry; Brazier, Michel; Mentaverri, Romuald; Zibara, Kazem; Kamel, Saı̈d

doi:10.1016/j.yjmcc.2019.01.021

Cited by 12 publications

(4 citation statements)

References 52 publications

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“…Proteomic specimens from the left atrial tissues were collected through animal atria/HL-1 cultures. Proteomic content was transferred to polyvinylidene fluoride membranes and analyzed through a proteomic assay kit (Bio-Rad™, Canada) via Western blotting following previously published literature [ 30 ]. The antibodies included CaMKII antibody (1 : 2000; Wanleibio, Shenyang, China), Ca v 1.2 antibody (1 : 1000; Abcam™, China), and GAPDH antibody (1 : 10000; ZSGB-BIO™, China).…”

Section: Methodsmentioning

confidence: 99%

Effects of Sacubitril/Valsartan on the Expression of CaMKII/Cav1.2 in Atrial Fibrillation Stimulation Rabbit Model

Lou

Liu

et al. 2022

BioMed Research International

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Background and Objective. Atrial fibrillation (AF) is linked to high morbidity and death rates throughout the world due to limited therapeutic options and thus presents a major challenge to the developed and developing countries. In this study, we aim to investigate the influence of sacubitril/valsartan (sac/val) treatment on the calmodulin-dependent protein kinase II (CaMKII)/Cav1.2 expression in AF models. Methods. Overall, 18 rabbits were randomly divided into control, pacing (600 beats/min), and pacing+sac/val groups. The rabbits in the pacing+sac/val cohort received oral sac/val (10 mg/kg twice daily) across the 21-day investigation period. After three weeks, the atrial effective refractory period (AERP) and AF induction rate were compared. HL-1 cultures were exposed to fast pacing (24 h) with and without LBQ657 (active sacubitril form)/valsartan. Western blots were used for detecting Cav1.2 and CaMKII expression within atrial muscles of the rabbits and HL-1 cultures of AF model. Results. In comparison to the sham cohort, the AF induction rate was markedly increased together with AERP reduction within pacing cohort. Such changes were markedly rescued through sac/val treatment in pacing+sac/val cohort. The proteomic expression profiles of CaMKII and Cav1.2 showed that the CaMKII expression was markedly upregulated, while Cav1.2 expression was downregulated in the pacing cohort. Importantly, these effects were absent in pacing+sac/val cohort. Conclusion. Results of this study show that sac/val treatment regulates the expression of CaMKII/Cav1.2 and could alter this pathway in atrial rapid electrical stimulation models. Therefore, this investigation could contribute to a novel strategy in AF therapeutics in clinical settings.

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Section: Methodsmentioning

confidence: 99%

Effects of Sacubitril/Valsartan on the Expression of CaMKII/Cav1.2 in Atrial Fibrillation Stimulation Rabbit Model

Lou

Liu

et al. 2022

BioMed Research International

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“…Dysfunctions in calcium regulatory proteins, including calcium-sensing receptors (CaSRs), calmodulin, and other associated molecules, lead to pathological calcification. It has been observed an increased CaSR expression in valvular interstitial cells (VICs) of calcified aortic valves and its modulation of CaSR expression in these cells has been shown to reduce calcium-induced valve calcification in vitro [ 89 ]. The upregulation of CaSR expression in VSMCs reduces cellular calcium deposition and difficulties in their transition to a calcifying phenotype [ 90 ].…”

Section: Molecular Networking In Vascular Calcificationmentioning

confidence: 99%

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities

Ortega,

De Leon-Oliva,

Gimeno-Longas

et al. 2024

Biomolecules

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Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43− and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

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“…Aortic calcification was assessed using Alizarin Red staining (Issa et al, 2019). Briefly, aortas were embedded in OCT compound and then frozen in cold (−80 • C) isopentane.…”

Section: Alizarin Red Stainingmentioning

confidence: 99%

GFOGER Peptide Modifies the Protein Content of Extracellular Vesicles and Inhibits Vascular Calcification

Mansour

Darwiche

Yaker

et al. 2020

Front. Cell Dev. Biol.

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ObjectiveVascular calcification (VC) is an active process during which vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and release extracellular vesicles (EVs). In turn, the EVs serve as calcification foci via interaction with type 1 collagen (COL1). We recently showed that a specific, six-amino-acid repeat (GFOGER) in the sequence of COL1 was involved in the latter’s interaction with integrins expressed on EVs. Our main objective was to test the GFOGER ability to inhibit VC.ApproachWe synthesized the GFOGER peptide and tested its ability to inhibit the inorganic phosphate (Pi)-induced calcification of VSMCs and aortic rings. Using mass spectrometry, we studied GFOGER’s effect on the protein composition of EVs released from Pi-treated VSMCs.ResultsCalcification of mouse VSMCs (MOVAS-1 cells), primary human VSMCs, and rat aortic rings was lower in the presence of GFOGER than with Pi alone (with relative decreases of 66, 58, and 91%, respectively; p < 0.001 for all) (no effect was observed with the scramble peptide GOERFG). A comparative proteomic analysis of EVs released from MOVAS-1 cells in the presence or absence of Pi highlighted significant differences in EVs’ protein content. Interestingly, the expression of some of the EVs’ proteins involved in the calcification process (such as osteogenic markers, TANK-binding kinase 1, and casein kinase II) was diminished in the presence of GFOGER peptide (data are available via ProteomeXchange with identifier PXD018169∗). The decrease of osteogenic marker expression observed in the presence of GFOGER was confirmed by q-RT-PCR analysis.ConclusionGFOGER peptide reduces vascular calcification by modifying the protein content of the subsequently released EVs, in particular by decreasing osteogenicswitching in VSMCs.

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Activation of the calcium-sensing receptor in human valvular interstitial cells promotes calcification

Cited by 12 publications

References 52 publications

Effects of Sacubitril/Valsartan on the Expression of CaMKII/Cav1.2 in Atrial Fibrillation Stimulation Rabbit Model

Effects of Sacubitril/Valsartan on the Expression of CaMKII/Cav1.2 in Atrial Fibrillation Stimulation Rabbit Model

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities

GFOGER Peptide Modifies the Protein Content of Extracellular Vesicles and Inhibits Vascular Calcification

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