Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease

Mantovani, Alessandro; Lunardi, Gianluigi; Bonapace, Stefano; Dugo, Clementina; Altomari, Anna; Molon, Giulio; Conti, Antonio; Bovo, Chiara; Laaksonen, Reijo; Byrne, Christopher D.; Bonnet, Fabrice; Targher, Giovanni

doi:10.1016/j.diabet.2020.03.003

Cited by 29 publications

(29 citation statements)

References 28 publications

(54 reference statements)

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“…Contrary to systemic levels, Cer(16:0) increases in the skin of patients with AD ( Berdyshev et al., 2018 ). The observed decreases in circulating Cer(16:0) levels in AD are inconsistent with reports indicating that this marker is altered (increased) in multiple other diseases such as neurodegenerative diseases ( Pujol-Lereis, 2019 ), acute ischemic stroke ( Gui et al., 2020 ), and chronic kidney disease ( Mantovani et al., 2021 ). Serum levels of Cer(16:0) in patients with uncontrolled asthma are higher than those in patients with controlled asthma ( Kim et al., 2020 ).…”

Section: Discussioncontrasting

confidence: 91%

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

et al. 2022

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Section: Discussioncontrasting

confidence: 91%

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

et al. 2022

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“…We provide evidence that the molecular cargo of PTEC‐derived apical sEV are promising urinary biomarker candidates for inflammatory kidney diseases. Notably, we also identified significantly elevated ceramide species (e.g., Cer d18:1/18:0, Cer d18:1/24:1) in basolateral inflammatory sEV that have been recently reported as increased in the circulation (plasma) of patients with chronic kidney disease (Mantovani et al., 2020) and may be of diagnostic utility in future validation studies. We also offer unique insights into the biological pathways through which polarized human PTEC mediate proximal‐to‐distal signalling (via apical sEV) and tubular‐immune cell communication (via basolateral sEV).…”

Section: Discussionsupporting

confidence: 66%

Molecular and functional profiling of apical versus basolateral small extracellular vesicles derived from primary human proximal tubular epithelial cells under inflammatory conditions

Wang

Wilkinson

Kildey

et al. 2021

J of Extracellular Vesicle

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Proximal tubular epithelial cells (PTEC) are central players in inflammatory kidney diseases. However, the complex signalling mechanism/s via which polarized PTEC mediate disease progression are poorly understood. Small extracellular vesicles (sEV), including exosomes, are recognized as fundamental components of cellular communication and signalling courtesy of their molecular cargo (lipids, microRNA, proteins). In this study, we examined the molecular content and function of sEV secreted from the apical versus basolateral surfaces of polarized human primary PTEC under inflammatory diseased conditions. PTEC were cultured under normal and inflammatory conditions on Transwell inserts to enable separate collection and isolation of apical/basolateral sEV. Significantly increased numbers of apical and basolateral sEV were secreted under inflammatory conditions compared with equivalent normal conditions. Multi‐omics analysis revealed distinct molecular profiles (lipids, microRNA, proteins) between inflammatory and normal conditions for both apical and basolateral sEV. Biological pathway analyses of significantly differentially expressed molecules associated apical inflammatory sEV with processes of cell survival and immunological disease, while basolateral inflammatory sEV were linked to pathways of immune cell trafficking and cell‐to‐cell signalling. In line with this mechanistic concept, functional assays demonstrated significantly increased production of chemokines (monocyte chemoattractant protein‐1, interleukin‐8) and immuno‐regulatory cytokine interleukin‐10 by peripheral blood mononuclear cells activated with basolateral sEV derived from inflammatory PTEC. We propose that the distinct molecular composition of sEV released from the apical versus basolateral membranes of human inflammatory PTEC may reflect specialized functional roles, with basolateral‐derived sEV pivotal in modulating tubulointerstitial inflammatory responses observed in many immune‐mediated kidney diseases. These findings provide a rationale to further evaluate these sEV‐mediated inflammatory pathways as targets for biomarker and therapeutic development.

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“…Also, C16-C20 saturated fatty acids 12 , such as palmitic acid, are increased in patients with CKD stage 5 compared with those with CKD stages 2-4. In addition to increased levels of free fatty acids, patients with CKD also have increased serum levels of ceramides, which are fatty acid derivatives 138 .…”

Section: Free Fatty Acidsmentioning

confidence: 99%

Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations

et al. 2021

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Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease

Cited by 29 publications

References 28 publications

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

Molecular and functional profiling of apical versus basolateral small extracellular vesicles derived from primary human proximal tubular epithelial cells under inflammatory conditions

Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations

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