Neutral sphingomyelinase‐2 and cardiometabolic diseases

Sindhu, Sardar; Leung, Yat Hei; Arefanian, Hossein; Al‐Mulla, Fahd; Ahmad, Rasheed; Prentki, Marc

doi:10.1111/obr.13248

Cited by 24 publications

(21 citation statements)

References 221 publications

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“…SM is primarily produced in the Golgi apparatus and transferred to all other cellular membranes ( Campelo et al, 2017 ). Sphingomyelinase catalyzes the hydrolysis of the phosphodiester bond of sphingomyelin and yields Cer and PC after stimulation by TNF-α or IL-1β ( Sindhu et al, 2021 ). In our sample, SM disorders dominated the lipid abnormalities observed in the MP subgroup and thus provide possible treatment targets for MP.…”

Section: Discussionmentioning

confidence: 99%

Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach

Dai

Wang

et al. 2022

Front. Mol. Biosci.

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Aim: Psoriasis vulgaris (PV) is a complicated autoimmune disease characterized by erythema of the skin and a lack of available cures. PV is associated with an increased risk of metabolic syndrome and cardiovascular disease, which are both mediated by the interaction between systemic inflammation and aberrant metabolism. However, whether there are differences in the lipid metabolism between different levels of severity of PV remains elusive. Hence, we explored the molecular evidence for the subtyping of PV according to alterations in lipid metabolism using serum metabolomics, with the idea that such subtyping may contribute to the development of personalized treatment.Methods: Patients with PV were recruited at a dermatology clinic and classified based on the presence of metabolic comorbidities and their Psoriasis Area and Severity Index (PASI) from January 2019 to November 2019. Age- and sex-matched healthy controls were recruited from the preventive health department of the same institution for comparison. We performed targeted metabolomic analyses of serum samples and determined the correlation between metabolite composition and PASI scores.Results: A total of 123 participants, 88 patients with PV and 35 healthy subjects, were enrolled in this study. The patients with PV were assigned to a “PVM group” (PV with metabolic comorbidities) or a “PV group” (PV without metabolic comorbidities) and further subdivided into a “mild PV” (MP, PASI <10) and a “severe PV” (SP, PASI ≥10) groups. Compared with the matched healthy controls, levels of 27 metabolites in the MP subgroup and 28 metabolites in the SP subgroup were found to be altered. Among these, SM (d16:0/17:1) and SM (d19:1/20:0) were positively correlated with the PASI in the MP subgroup, while Cer (d18:1/18:0), PC (18:0/22:4), and PC (20:0/22:4) were positively correlated with the PASI in the SP subgroup. In the PVM group, levels of 17 metabolites were increased, especially ceramides and phosphatidylcholine, compared with matched patients from the PV group. In addition, the correlation analysis indicated that Cer (d18:1/18:0) and SM (d16:1/16:1) were not only correlated with PASI but also has strongly positive correlations with biochemical indicators.Conclusion: The results of this study indicate that patients with PV at different severity levels have distinct metabolic profiles, and that metabolic disorders complicate the disease development. These findings will help us understand the pathological progression and establish strategies for the precision treatment of PV.

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Section: Discussionmentioning

confidence: 99%

Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach

Dai

Wang

et al. 2022

Front. Mol. Biosci.

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“…Neural sphingomyelinase 2 (nSMase2) is a hydrolase enzyme that involved in sphingolipid metabolism reactions ( Sindhu et al, 2021 ). Nobuyoshi Kosaka et al demonstrated that inhibiting the activity of nSMase2 lead to reduced exosomal miRNA secretion.…”

Section: Exosomal Microrna: Biogenesismentioning

confidence: 99%

Exosomal MiRNAs in Osteosarcoma: Biogenesis and Biological Functions

Tang

Feng

et al. 2022

Front. Pharmacol.

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MiRNAs are a group of non-coding RNA molecules that function in mRNA translational inhibition via base-pairing with complementary sequences in target mRNA. In oncology, miRNAs have raised great attention due to their aberrant expression and pivotal roles in the pathogenesis of multiple malignancies including osteosarcoma. MiRNAs can be transported by exosome, the nano-extracellular vesicle with a diameter of 30–150 nm. Recently, a growing number of studies have demonstrated that exosomal miRNAs play a critical role in tumor initiation and progression, by exerting multiple biological functions including metastasis, angiogenesis, drug resistance and immunosuppression. In this review, we aim to depict the biogenesis of exosomal miRNAs and summarize the potential diagnostic and therapeutic functions of exosomal miRNAs in osteosarcoma.

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“…The phosphorylation of sphingosineby-sphingosine kinases (SphK1 and SphK2) produces sphingosine 1-phosphaet (S1P), a molecule involved in angiogenesis, proliferation, migration, transformation, and inflammation of cells. This SL turnover pathway has been estimated to contribute from 50% up to 90% of the ceramide biosynthesis [31,32]. The salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals [33].…”

Section: Ceramidesmentioning

confidence: 99%

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATS) are worldwide known diseases with increased incidence and prevalence. These two are driven and are interconnected by multiple oxidative and metabolic functions such as lipotoxicity. A gamut of evidence suggests that sphingolipids (SL), such as ceramides, account for much of the tissue damage. Although in humans they are proving to be accurate biomarkers of adverse cardiovascular disease outcomes and NAFLD progression, in rodents, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of metabolic driven diseases such as diabetes, ATS, and hepatic steatosis. In this narrative review, we discuss the pathways which generate the ceramide synthesis, the potential use of circulating ceramides as novel biomarkers in the development and progression of ATS and related diseases, and their potential use as therapeutic targets in NAFDL-ATS development which can further provide new clues in this field.

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Neutral sphingomyelinase‐2 and cardiometabolic diseases

Cited by 24 publications

References 221 publications

Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach

Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach

Exosomal MiRNAs in Osteosarcoma: Biogenesis and Biological Functions

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

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