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Cardiovascular disease is highly prevalent in patients with chronic kidney disease. Hyperphosphatemia is associated with subclinical atheromatosis in chronic kidney disease. Phosphate-induced endothelial dysfunction and vascular calcification are thought to be key inducers of atherosclerosis in this condition. Zhou et al. now demonstrate that phosphate promotes de novo cholesterol synthesis in vascular smooth muscle and macrophages through increased 3-hydroxy-3-methylglutaryl coenzyme A reductase activation. This observation may change current concepts of atherosclerosis development and management in chronic kidney disease.
Lucie Hénaut; Ziad A. Massy. Phosphate meeting cholesterol—consequences for cardiovascular disease in chronic kidney disease? Kidney International 2021, 99, 1264 -1267.
AMA StyleLucie Hénaut, Ziad A. Massy. Phosphate meeting cholesterol—consequences for cardiovascular disease in chronic kidney disease? Kidney International. 2021; 99 (6):1264-1267.
Chicago/Turabian StyleLucie Hénaut; Ziad A. Massy. 2021. "Phosphate meeting cholesterol—consequences for cardiovascular disease in chronic kidney disease?" Kidney International 99, no. 6: 1264-1267.
Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.
Maria Grissi; Cédric Boudot; Maryam Assem; Alexandre Candellier; Mathilde Lando; Sabrina Poirot-Leclercq; Agnès Boullier; Youssef Bennis; Gaëlle Lenglet; Carine Avondo; Jean-Daniel Lalau; Gabriel Choukroun; Ziad A. Massy; Saïd Kamel; Jean-Marc Chillon; Lucie Hénaut. Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease. Scientific Reports 2021, 11, 1 -14.
AMA StyleMaria Grissi, Cédric Boudot, Maryam Assem, Alexandre Candellier, Mathilde Lando, Sabrina Poirot-Leclercq, Agnès Boullier, Youssef Bennis, Gaëlle Lenglet, Carine Avondo, Jean-Daniel Lalau, Gabriel Choukroun, Ziad A. Massy, Saïd Kamel, Jean-Marc Chillon, Lucie Hénaut. Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease. Scientific Reports. 2021; 11 (1):1-14.
Chicago/Turabian StyleMaria Grissi; Cédric Boudot; Maryam Assem; Alexandre Candellier; Mathilde Lando; Sabrina Poirot-Leclercq; Agnès Boullier; Youssef Bennis; Gaëlle Lenglet; Carine Avondo; Jean-Daniel Lalau; Gabriel Choukroun; Ziad A. Massy; Saïd Kamel; Jean-Marc Chillon; Lucie Hénaut. 2021. "Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease." Scientific Reports 11, no. 1: 1-14.
Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions.
Lucie Hénaut; Alexandre Candellier; Cédric Boudot; Maria Grissi; Romuald Mentaverri; Gabriel Choukroun; Michel Brazier; Saïd Kamel; Ziad A. Massy. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. Toxins 2019, 11, 529 .
AMA StyleLucie Hénaut, Alexandre Candellier, Cédric Boudot, Maria Grissi, Romuald Mentaverri, Gabriel Choukroun, Michel Brazier, Saïd Kamel, Ziad A. Massy. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. Toxins. 2019; 11 (9):529.
Chicago/Turabian StyleLucie Hénaut; Alexandre Candellier; Cédric Boudot; Maria Grissi; Romuald Mentaverri; Gabriel Choukroun; Michel Brazier; Saïd Kamel; Ziad A. Massy. 2019. "New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease." Toxins 11, no. 9: 529.
Ischemic stroke is highly prevalent in chronic kidney disease (CKD) patients and has been associated with a higher risk of neurological deterioration and in-hospital mortality. To date, little is known about the processes by which CKD worsens ischemic stroke. This work aimed to investigate the cellular and molecular mechanism associated with ischemic stroke severity in an in vivo model of CKD. CKD was induced through right kidney cortical electrocautery in 8-week-old female C57BL/6 J mice followed by left total nephrectomy. Transient middle cerebral artery occlusion (tMCAO) was performed 6 weeks after left nephrectomy. Twenty-four hours after tMCAO, the infarct volumes were significantly wider in CKD than in SHAM mice. CKD mice displayed decreased neuroscore, impaired ability to remain on rotarod device, weaker muscular strength and decreased prehensile score. Apoptosis, neuronal loss, glial cells recruitment and microglia/macrophages M1 signature genes CD32, CD86, IL-1β, IL-6, MCP1 and iNOS were significantly increased within ischemic lesions of CKD mice. This effect was associated with decreased AMP kinase phosphorylation and increased activation of the NFΚB pathway. Pharmacological targeting of AMP kinase activity, which is known to block microglia/macrophages M1 polarization, appears promising to improve stroke recovery in CKD.
Lucie Hénaut; Maria Grissi; François Brazier; Maryam Assem; Sabrina Poirot-Leclercq; Gaëlle Lenglet; Cédric Boudot; Carine Avondo; Agnès Boullier; Gabriel Choukroun; Ziad. A Massy; Saïd Kamel; Jean-Marc Chillon. Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease. Scientific Reports 2019, 9, 6432 .
AMA StyleLucie Hénaut, Maria Grissi, François Brazier, Maryam Assem, Sabrina Poirot-Leclercq, Gaëlle Lenglet, Cédric Boudot, Carine Avondo, Agnès Boullier, Gabriel Choukroun, Ziad. A Massy, Saïd Kamel, Jean-Marc Chillon. Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease. Scientific Reports. 2019; 9 (1):6432.
Chicago/Turabian StyleLucie Hénaut; Maria Grissi; François Brazier; Maryam Assem; Sabrina Poirot-Leclercq; Gaëlle Lenglet; Cédric Boudot; Carine Avondo; Agnès Boullier; Gabriel Choukroun; Ziad. A Massy; Saïd Kamel; Jean-Marc Chillon. 2019. "Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease." Scientific Reports 9, no. 1: 6432.
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Low-grade systemic inflammation, which is frequently observed in such patients, is an independent risk factor for cardiovascular morbidity and mortality [1]. High circulating levels of inflammation markers are known to be associated with increased prevalence, severity and progression of vascular calcification [2] and in turn, vascular calcification also is associated with excess cardiovascular mortality in CKD. Experimental studies suggest that the nature of the association between low-grade systemic inflammation and vascular calcification is causal [3]. If confirmed in humans, this could have major therapeutic consequences. To date, the molecular mechanisms involved remain incompletely understood.
Lucie Hénaut; Ziad A Massy. New insights into the key role of interleukin 6 in vascular calcification of chronic kidney disease. Nephrology Dialysis Transplantation 2018, 33, 543 -548.
AMA StyleLucie Hénaut, Ziad A Massy. New insights into the key role of interleukin 6 in vascular calcification of chronic kidney disease. Nephrology Dialysis Transplantation. 2018; 33 (4):543-548.
Chicago/Turabian StyleLucie Hénaut; Ziad A Massy. 2018. "New insights into the key role of interleukin 6 in vascular calcification of chronic kidney disease." Nephrology Dialysis Transplantation 33, no. 4: 543-548.