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Isabelle Six
UR 7517 UPJV, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications (MP3CV), Picardie Jules Verne University, 80025 Amiens, France

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Review
Published: 18 June 2020 in Toxins
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Vascular dysfunction is an essential element found in many cardiovascular pathologies and in pathologies that have a cardiovascular impact such as chronic kidney disease (CKD). Alteration of vasomotricity is due to an imbalance between the production of relaxing and contracting factors. In addition to becoming a determining factor in pathophysiological alterations, vascular dysfunction constitutes the first step in the development of atherosclerosis plaques or vascular calcifications. In patients with CKD, alteration of vasomotricity tends to emerge as being a new, less conventional, risk factor. CKD is characterized by the accumulation of uremic toxins (UTs) such as phosphate, para-cresyl sulfate, indoxyl sulfate, and FGF23 and, consequently, the deleterious role of UTs on vascular dysfunction has been explored. This accumulation of UTs is associated with systemic alterations including inflammation, oxidative stress, and the decrease of nitric oxide production. The present review proposes to summarize our current knowledge of the mechanisms by which UTs induce vascular dysfunction.

ACS Style

Isabelle Six; Nadia Flissi; Gaëlle Lenglet; Loïc Louvet; Said Kamel; Marlène Gallet; Ziad A. Massy; Sophie Liabeuf. Uremic Toxins and Vascular Dysfunction. Toxins 2020, 12, 1 .

AMA Style

Isabelle Six, Nadia Flissi, Gaëlle Lenglet, Loïc Louvet, Said Kamel, Marlène Gallet, Ziad A. Massy, Sophie Liabeuf. Uremic Toxins and Vascular Dysfunction. Toxins. 2020; 12 (6):1.

Chicago/Turabian Style

Isabelle Six; Nadia Flissi; Gaëlle Lenglet; Loïc Louvet; Said Kamel; Marlène Gallet; Ziad A. Massy; Sophie Liabeuf. 2020. "Uremic Toxins and Vascular Dysfunction." Toxins 12, no. 6: 1.

Journal article
Published: 17 June 2020 in International Journal of Molecular Sciences
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This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes endothelium-derived epoxyeicosatrienoic acids, plays a role in vascular calcification. The sEH inhibitor trans-4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid (t-AUCB) potentiated the increase in calcium deposition of rat aortic rings cultured in high-phosphate conditions. This was associated with increased tissue-nonspecific alkaline phosphatase activity and mRNA expression level of the osteochondrogenic marker Runx2. The procalcifying effect of t-AUCB was prevented by mechanical aortic deendothelialization or inhibition of the production and action of epoxyeicosatrienoic acids using the cytochrome P450 inhibitor fluconazole and the antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE), respectively. Similarly, exogenous epoxyeicosatrienoic acids potentiated the calcification of rat aortic rings through a protein kinase A (PKA)-dependent mechanism and of human aortic vascular smooth muscle cells when sEH was inhibited by t-AUCB. Finally, a global gene expression profiling analysis revealed that the mRNA expression level of sEH was decreased in human carotid calcified plaques compared to adjacent lesion-free sites and was inversely correlated with Runx2 expression. These results show that sEH hydrolase plays a protective role against vascular calcification by reducing the bioavailability of epoxyeicosatrienoic acids.

ACS Style

Olivier Varennes; Romuald Mentaverri; Thomas Duflot; Gilles Kauffenstein; Thibaut Objois; Gaëlle Lenglet; Carine Avondo; Christophe Morisseau; Michel Brazier; Saïd Kamel; Isabelle Six; Jeremy Bellien. The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification. International Journal of Molecular Sciences 2020, 21, 1 .

AMA Style

Olivier Varennes, Romuald Mentaverri, Thomas Duflot, Gilles Kauffenstein, Thibaut Objois, Gaëlle Lenglet, Carine Avondo, Christophe Morisseau, Michel Brazier, Saïd Kamel, Isabelle Six, Jeremy Bellien. The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification. International Journal of Molecular Sciences. 2020; 21 (12):1.

Chicago/Turabian Style

Olivier Varennes; Romuald Mentaverri; Thomas Duflot; Gilles Kauffenstein; Thibaut Objois; Gaëlle Lenglet; Carine Avondo; Christophe Morisseau; Michel Brazier; Saïd Kamel; Isabelle Six; Jeremy Bellien. 2020. "The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification." International Journal of Molecular Sciences 21, no. 12: 1.

Journal article
Published: 12 June 2020 in Revue Francophone des Laboratoires
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Au niveau de la paroi vasculaire, on peut distinguer de la périphérie du vaisseau vers la lumière, l’adventice, la média composée essentiellement de cellules musculaires lisses et l’intima composée essentiellement de cellules endothéliales. La vasomotricité est la capacité du vaisseau à se contracter et à se relâcher. Pour cela, l’endothélium répond à des stimuli et les traduit en réponses biologiques qui seront transmises au muscle lisse. Le muscle lisse possède également l’ensemble des systèmes lui permettant de se contracter ou de se relâcher indépendamment des signaux produits par l’endothélium. On distingue donc une vasomotricité liée à l’action directe du muscle lisse et une vasomotricité dépendante de l’endothélium. Les réponses vasomotrices du muscle lisse sont liées à l’activation de voies de signalisation entraînant des variations de concentrations de calcium intracellulaire. L’augmentation de calcium résultant entraîne une vasoconstriction alors que la diminution de calcium entraîne une vasorelaxation. La vasoconstriction dépendante de l’endothélium est liée à la production de facteurs produits par l’endothélium (les dérivés du métabolisme de l’acide arachidonique : les endoperoxydes, le thromboxane A2, la prostaglandine H2, l’endothéline, les ROS (Reactive Oxygen Species, espèces réactives de l'oxygène) et l’angiotensine II) entraînant une contraction du muscle lisse. Les cellules endothéliales sont capables de moduler la vasomotricité grâce à la production de facteurs vasodilatateurs que sont la prostacycline (PG12), le monoxyde d'azote (NO) et le facteur hyperpolarisant dérivé de l'endothélium (EDHF, endothelium derived hyperpolarizing factor). La fonction vasculaire et son maintien sont un élément essentiel garantissant la santé du vaisseau. The vascular wall is composed of three structures from the periphery to the lumen of the vessel, the adventitia, the media composed mainly of smooth muscle cells and the intima composed essentially of endothelial cells. Vasomotricity is the capacity of vessel to contract or relax. For this the endothelium responds to stimuli and translates them into biological responses transmitted to the smooth muscle. The smooth muscle also has all the systems that allow it to contract or relax regardless of the signals produced by the endothelium. This distinguishes vasomotricity due to the direct action of the smooth muscle and a vasomotricity dependent on endothelium. The vasomotor responses of the smooth muscle are related to the activation of signaling pathways resulting in variations in intracellular calcium concentrations. The resulting increase in calcium leads to vasoconstriction, while decreased calcium leads to vasorelaxation. The endothelium dependent vasoconstriction is linked to the production of factors produced by endothelium (derivatives of arachidonic acid metabolism: endoperoxides, thromboxane A2, prostaglandin H2, endothelin, ROS (Reactive oxygen species) and angiotensin II) resulting in a contraction of the smooth muscle. Endothelial cells are able to modulate vasomotricity through the production of vasodilator factors such as prostacyclin (PGI2), nitric oxide (NO) and endothelium derived hyperpolarizing factor (EDHF). Vascular function and its maintenance is an essential element in ensuring the health of the vessel.

ACS Style

Isabelle Six; Jean Marc Chillon; Saïd Kamel. La structure et la fonction vasculaires. Revue Francophone des Laboratoires 2020, 2020, 30 -39.

AMA Style

Isabelle Six, Jean Marc Chillon, Saïd Kamel. La structure et la fonction vasculaires. Revue Francophone des Laboratoires. 2020; 2020 (523):30-39.

Chicago/Turabian Style

Isabelle Six; Jean Marc Chillon; Saïd Kamel. 2020. "La structure et la fonction vasculaires." Revue Francophone des Laboratoires 2020, no. 523: 30-39.

Journal article
Published: 01 June 2017 in Revue Francophone des Laboratoires
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ACS Style

Olivier Varennes; Isabelle Six; Romuald Mentaverri; Said Kamel. Mécanismes physiopathologiques du rétrécissement aortique calcifié. Revue Francophone des Laboratoires 2017, 2017, 25 -32.

AMA Style

Olivier Varennes, Isabelle Six, Romuald Mentaverri, Said Kamel. Mécanismes physiopathologiques du rétrécissement aortique calcifié. Revue Francophone des Laboratoires. 2017; 2017 (493):25-32.

Chicago/Turabian Style

Olivier Varennes; Isabelle Six; Romuald Mentaverri; Said Kamel. 2017. "Mécanismes physiopathologiques du rétrécissement aortique calcifié." Revue Francophone des Laboratoires 2017, no. 493: 25-32.

Journal article
Published: 01 March 2017 in Joint Bone Spine
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Our results indicate that CaSR expression in synovial derived monocytes is higher in osteoarthritis than in inflammatory rheumatisms and that CaSR expression is modulated by the nature of the synovial fluid. Given the role played by monocytes in the pathogenesis of chronic rheumatisms, monocytes could be interesting therapeutic targets via the CaSR.

ACS Style

Alice Séjourné; Cédric Boudot; Thibaut Objois; Patrice Fardellone; Michel Brazier; Isabelle Six; Saïd Kamel; Romuald Mentaverri; Vincent Goeb. Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis. Joint Bone Spine 2017, 84, 175 -181.

AMA Style

Alice Séjourné, Cédric Boudot, Thibaut Objois, Patrice Fardellone, Michel Brazier, Isabelle Six, Saïd Kamel, Romuald Mentaverri, Vincent Goeb. Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis. Joint Bone Spine. 2017; 84 (2):175-181.

Chicago/Turabian Style

Alice Séjourné; Cédric Boudot; Thibaut Objois; Patrice Fardellone; Michel Brazier; Isabelle Six; Saïd Kamel; Romuald Mentaverri; Vincent Goeb. 2017. "Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis." Joint Bone Spine 84, no. 2: 175-181.

Review
Published: 14 November 2016 in Current Vascular Pharmacology
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ACS Style

Tanja Celic; Valérie Metzinger-Le Meuth; Isabelle Six; Ziad A Massy; Laurent Metzinger. The mir-221/222 Cluster is a Key Player in Vascular Biology via the Fine-Tuning of Endothelial Cell Physiology. Current Vascular Pharmacology 2016, 15, 40 -46.

AMA Style

Tanja Celic, Valérie Metzinger-Le Meuth, Isabelle Six, Ziad A Massy, Laurent Metzinger. The mir-221/222 Cluster is a Key Player in Vascular Biology via the Fine-Tuning of Endothelial Cell Physiology. Current Vascular Pharmacology. 2016; 15 (1):40-46.

Chicago/Turabian Style

Tanja Celic; Valérie Metzinger-Le Meuth; Isabelle Six; Ziad A Massy; Laurent Metzinger. 2016. "The mir-221/222 Cluster is a Key Player in Vascular Biology via the Fine-Tuning of Endothelial Cell Physiology." Current Vascular Pharmacology 15, no. 1: 40-46.

Journal article
Published: 01 November 2015 in Atherosclerosis
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In chronic kidney disease (CKD), blood vessels are permanently exposed to uremic toxins such as indoxyl sulfate (IS). We hypothesized that IS could alter vascular tone and that reducing its serum concentration could be beneficial. We studied acute and longer-term effects of IS and AST-120, an oral charcoal adsorbent, on vascular reactivity, endothelium integrity and expression of adhesion molecules VCAM-1 and ICAM-1 in aortic rings of normal and uremic wild type (WT) mice in vitro, and the cardiovascular effects of AST-120 in both WT and apoE-/- mice with CKD in vivo. In vitro, 1.0 mM IS acutely reduced vascular relaxation (64% for IS 1.0 mM vs. 80% for control, p < 0.05). The effect was more marked after 4 days exposure (39% for IS 1.0 mM 4 days; p < 0.001, prolonged vs. acute exposure), and was associated with endothelial cell loss and upregulation of ICAM-1/VCAM-1 expression. In vitro, AST-120 restored normal vascular function and prevented IS induced endothelial cell loss and ICAM-1/VCAM-1 upregulation. In vivo, AST-120 treatment of CKD mice (1) improved vascular relaxation (72% vs. 48% maximal relaxation in treated vs. untreated mice, p < 0.001), (2) reduced aortic VCAM-1 and ICAM-1 expression, (3) decreased aorta systolic expansion rate (9 ± 3% CKD vs. 14 ± 3% CKD + AST-120, p < 0.02), and (4) prevented the increase in pulse wave velocity (3.56 ± 0.17 m/s CKD vs. 3.10 ± 0.08 m/s CKD + AST-120, p < 0.006). Similar changes were observed in apoE-/- mice. IS appears to be an important contributor to the vascular dysfunction associated with CKD. AST-120 treatment ameliorates this dysfunction, possibly via a decrease in serum IS concentration.

ACS Style

Isabelle Six; Priscilla Gross; Mathieu Rémond; Jean Marc Chillon; Sabrina Poirot; Tilman B. Drueke; Ziad A. Massy. Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120. Atherosclerosis 2015, 243, 248 -256.

AMA Style

Isabelle Six, Priscilla Gross, Mathieu Rémond, Jean Marc Chillon, Sabrina Poirot, Tilman B. Drueke, Ziad A. Massy. Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120. Atherosclerosis. 2015; 243 (1):248-256.

Chicago/Turabian Style

Isabelle Six; Priscilla Gross; Mathieu Rémond; Jean Marc Chillon; Sabrina Poirot; Tilman B. Drueke; Ziad A. Massy. 2015. "Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120." Atherosclerosis 243, no. 1: 248-256.

Journal article
Published: 01 November 2015 in Revue Francophone des Laboratoires
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Par ses implications dans de nombreuses réactions biologiques et son rôle capital dans la structure du squelette, le phosphate apporté par notre alimentation, est indispensable à la vie. La phosphatémie, marqueur de la charge phosphatée de l’organisme, est maintenue dans des limites physiologiques grâce à des systèmes hormonaux agissant de concert sur l’intestin et le rein. L’hyperphosphatémie est considérée aujourd’hui comme un important facteur de risque non-traditionnel, prédictif de la morbi-mortalité cardiovasculaire. Plusieurs études épidémiologiques et expérimentales récentes ont en effet démontré un lien positif entre les concentrations sériques élevées de phosphate et la survenue de différentes maladies cardiovasculaires. Le phosphate, par des effets à la fois directs et indirects, est capable d’accélérer le processus de calcification vasculaire, d’induire une dysfonction endothéliale et une hypertrophie ventriculaire gauche, contribuant ainsi au risque cardiovasculaire. Le lien entre phosphatémie et événements cardiovasculaires a été mis en évidence non seulement dans la maladie rénale chronique, condition pathologique qui s’accompagne fréquemment d’une hyperphosphatémie, mais également, et de façon plus surprenante, dans la population générale, pour laquelle des valeurs de phosphate sérique situées autour de la limite supérieure de la normale, sont également prédictives d’accidents cardiovasculaires. Cette relation n’est pas encore clairement comprise, mais pourrait s’expliquer par l’augmentation constatée au cours de ces dernières années, de l’apport de phosphate inorganique alimentaire, présent dans les aliments transformés contenant des additifs phosphatés. Des stratégies préventives et curatives de l’hyperphosphatémie basées sur des régimes alimentaires ou sur l’utilisation de substances thérapeutiques visant à diminuer l’absorption intestinale des phosphates sont mises en place aujourd’hui, en particulier dans la maladie rénale chronique. De futures études seront encore nécessaires pour préciser le rôle de l’excès de phosphates alimentaires sur le système cardiovasculaire et l’intérêt d’utiliser des stratégies préventives et thérapeutiques dans la population générale. Phosphate is an essential mineral that plays a key role in human body. Phosphatemia, which can reflect the pool of phosphate, is maintained within a normal range thanks to a tight hormonal regulation. Several recent epidemiological and experimental studies have demonstrated that hyperphosphatemia is associated with increased risk of cardiovascular disease and mortality. Indeed, phosphate can exert deleterious effect directly or indirectly on cardiovascular system by accelerating cardiovascular calcification, promoting endothelial dysfunction and left ventricular hypertrophy. The association between phosphate and cardiovascular risk has been found in patients with chronic kidney disease, a pathological condition where hyperphosphatemia is frequent, due to an unbalance in mineral metabolism. More surprisingly, this association has been also established among people without chronic kidney disease. In the general population, studies have reported an increased risk of cardiovascular disease even at modestly elevated phosphatemia. The reason of this association is not yet clear, but could be due to, at least in part, to the increasing dietary intake of phosphate linked to a greater consumption of processed foods with phosphate additives. A better understanding of mechanisms of impaired phosphate metabolism in CKD as well as in the general population would help to clarify the possible role of excess dietary phosphate as a health risk factor.

ACS Style

Haifa Rahabi-Layachi; Isabelle Six; Said Kamel. L’excès de phosphate peut-il s’avérer aussi dangereux pour le système cardiovasculaire que l’excès de cholestérol ? Revue Francophone des Laboratoires 2015, 2015, 27 -34.

AMA Style

Haifa Rahabi-Layachi, Isabelle Six, Said Kamel. L’excès de phosphate peut-il s’avérer aussi dangereux pour le système cardiovasculaire que l’excès de cholestérol ? Revue Francophone des Laboratoires. 2015; 2015 (476):27-34.

Chicago/Turabian Style

Haifa Rahabi-Layachi; Isabelle Six; Said Kamel. 2015. "L’excès de phosphate peut-il s’avérer aussi dangereux pour le système cardiovasculaire que l’excès de cholestérol ?" Revue Francophone des Laboratoires 2015, no. 476: 27-34.

Journal article
Published: 24 August 2015 in Journal of Cellular Physiology
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Chronic kidney disease (CKD) is characterized by vascular remodeling and the retention of uremic toxins, several of which are independently associated with the high cardiovascular mortality rate in CKD patients. Whether the association between these uremic toxins and cardiovascular mortality is due to induction of vascular dysfunction and resulting vascular remodeling remains to be determined. This study evaluates the effects of para‐cresyl sulfate (PCS), a newly identified uremic toxin, on vascular function and remodeling. PCS acutely induced oxidative stress in both endothelial and vascular smooth muscle cells, with a maximal effect at 0.15 mM, corresponding to the mean ‘uremic’ concentration found in dialysis patients. PCS significantly increased within 30 min phenylephrine‐induced contraction of mouse thoracic aorta, through direct activation of rho‐kinase, independently of oxidative stress induction, as demonstrated by the capacity of rho‐kinase inhibitor Y‐27632 to abolish this effect. After exposure of the aorta to PCS for 48 h, we observed inward eutrophic remodeling, a hallmark of uremic vasculopathy characterized by a reduction of the area of both lumen and media, with unchanged media/lumen ratio. In conclusion, elevated PCS concentrations such as those observed in CKD patients, by promoting both vascular dysfunction and vascular remodeling, may contribute to the development of hypertension and to cardiovascular mortality in CKD. This article is protected by copyright. All rights reserved

ACS Style

Priscilla Gross; Ziad A. Massy; Lucie Henaut; Cédric Boudot; Joanna Cagnard; Cécilia March; Saïd Kamel; Tilman B. Drueke; Isabelle Six. Para-cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling. Journal of Cellular Physiology 2015, 230, 2927 -2935.

AMA Style

Priscilla Gross, Ziad A. Massy, Lucie Henaut, Cédric Boudot, Joanna Cagnard, Cécilia March, Saïd Kamel, Tilman B. Drueke, Isabelle Six. Para-cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling. Journal of Cellular Physiology. 2015; 230 (12):2927-2935.

Chicago/Turabian Style

Priscilla Gross; Ziad A. Massy; Lucie Henaut; Cédric Boudot; Joanna Cagnard; Cécilia March; Saïd Kamel; Tilman B. Drueke; Isabelle Six. 2015. "Para-cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling." Journal of Cellular Physiology 230, no. 12: 2927-2935.

Journal article
Published: 01 June 2015 in Endocrinology
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Vascular calcification (VC) is a degenerative disease that contributes to cardiovascular morbidity and mortality. A negative relationship has been demonstrated between VC and calcium sensing receptor (CaSR) expression in the vasculature. Of interest, vitamin D response elements, which allow responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are present in the promoters of the CaSR gene. We hypothesized that 1,25(OH)2D3, by modulating CaSR expression in vascular smooth muscle cells (VSMCs), might protect against VC. Human VSMCs were exposed to increasing concentrations of 1,25(OH)2D3 (0.01–10 nmol/L) in noncalcifying (1.8 mmol/L) or procalcifying Ca2+0 condition (5.0 mmol/L). Using quantitative RT-PCR and Western blotting we observed a significant increase in both CaSR mRNA and protein levels after exposure to 1.0 nmol/L 1,25(OH)2D3. This effect was associated with a maximal increase in CaSR expression at the cell surface after 48 hours of 1,25(OH)2D3 treatment, as assessed by flow cytometry. Down-regulation of the vitamin D receptor by small interfering RNA abolished these effects. In the procalcifying condition, 1.0 nmol/L 1,25(OH)2D3 blocked the Ca2+0-induced decrease in total and surface CaSR expression and protected against mineralization. Down-regulation of CaSR expression by CaSR small interfering RNA abolished this protective effect. 1,25(OH)2D3 concentrations of 0.5 and 5.0 nmol/L were also effective, but other (0.01, 0.1, and 10 nmol/L) concentrations did not modify CaSR expression and human VSMC mineralization. In conclusion, these findings suggest that nanomolar concentrations of 1,25(OH)2D3 induce a CaSR-dependent protection against VC. Both lower and higher concentrations are either ineffective or may even promote VC. Whether this also holds true in the clinical setting requires further study.

ACS Style

Aurélien Mary; Lucie Hénaut; Cédric Boudot; Isabelle Six; Michel Brazier; Ziad A. Massy; Tilman B. Drueke; Saïd Kamel; Romuald Mentaverri. Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression. Endocrinology 2015, 156, 1965 -1974.

AMA Style

Aurélien Mary, Lucie Hénaut, Cédric Boudot, Isabelle Six, Michel Brazier, Ziad A. Massy, Tilman B. Drueke, Saïd Kamel, Romuald Mentaverri. Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression. Endocrinology. 2015; 156 (6):1965-1974.

Chicago/Turabian Style

Aurélien Mary; Lucie Hénaut; Cédric Boudot; Isabelle Six; Michel Brazier; Ziad A. Massy; Tilman B. Drueke; Saïd Kamel; Romuald Mentaverri. 2015. "Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression." Endocrinology 156, no. 6: 1965-1974.

Journal article
Published: 01 September 2013 in Kidney International
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Elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease (CVD) in patients with chronic renal failure (CRF). The phosphate-binder sevelamer has been shown to decrease both phosphate and FGF23, but limited data indicate that sevelamer improves CRF-related CVD, such as diastolic dysfunction, left ventricular hypertrophy (LVH), and aortic stiffness. To gain additional information, we measured the effects of sevelamer on CVD in a murine model of CRF. Groups of CRF and sham-operated mice received regular chow or 3% sevelamer-HCl in the chow for 14 weeks, starting 6 weeks after the initiation of CRF or sham operation. After the first 8 weeks of sevelamer treatment, CRF mice had decreased serum phosphate levels and an improved aortic systolic expansion rate, pulse-wave velocity, and diastolic function, although LVH remained unchanged. Following an additional 6-week course of sevelamer, LVH had not progressed. The FGF23 serum level was not reduced by sevelamer until after 14 weeks of treatment. In multiple regression analysis, serum phosphate, but not FGF23, was independently correlated with LV diastolic function and mass. Thus, sevelamer first improved aortic stiffness and diastolic dysfunction and secondarily prevented LVH in mice with CRF. The phosphate-lowering, rather than FGF23-lowering, effect appears to be responsible for the observed cardiovascular improvement.

ACS Style

Julien Maizel; Isabelle Six; Sebastien Dupont; Edouard Secq; Benedicte Dehedin; Fellype C. Barreto; Joyce Benchitrit; Sabrina Poirot; Michel Slama; Christophe Tribouilloy; Gabriel Choukroun; Jean C. Mazière; Tilman B. Drueke; Ziad A. Massy. Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure. Kidney International 2013, 84, 491 -500.

AMA Style

Julien Maizel, Isabelle Six, Sebastien Dupont, Edouard Secq, Benedicte Dehedin, Fellype C. Barreto, Joyce Benchitrit, Sabrina Poirot, Michel Slama, Christophe Tribouilloy, Gabriel Choukroun, Jean C. Mazière, Tilman B. Drueke, Ziad A. Massy. Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure. Kidney International. 2013; 84 (3):491-500.

Chicago/Turabian Style

Julien Maizel; Isabelle Six; Sebastien Dupont; Edouard Secq; Benedicte Dehedin; Fellype C. Barreto; Joyce Benchitrit; Sabrina Poirot; Michel Slama; Christophe Tribouilloy; Gabriel Choukroun; Jean C. Mazière; Tilman B. Drueke; Ziad A. Massy. 2013. "Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure." Kidney International 84, no. 3: 491-500.