Dataset Information

Tandem proteomic and N-glycoproteomic analysis of extracellular vesicles

ABSTRACT: Extracellular vesicles (EVs) derived from diverse biofluids have emerged as promising noninvasive diagnostic biomarkers or signatures for various diseases. EV-associated N-glycoproteins are crucial for the biological functions of EVs and hold significant potential for disease diagnosis and prognosis. However, analyzing changes in EV N-glycoproteins from ultratrace samples presents considerable challenges. This study introduces a robust method, which utilizes magnetic nanochains to sensitively enrich EV N-glycoproteins in a single tube.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xuejiang Guo

PROVIDER: PXD057512 | iProX | Tue Nov 05 00:00:00 GMT 2024

REPOSITORIES: iProX

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A functionally tunable magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids.

Li Mingyang M Song Xiaorong X Tu Haixia H Sun Jie J Deng Yuanyuan Y Wang Bing B Cai Yuhan Y Wang Yulian Y Li Bin B Wang Yue Y Zhang Xiangzheng X Wei Dong D Yang Xiaoyu X Guo Yueshuai Y Li Xiang X Gu Jie J Ni Jie J Zhou Yifan Y Gu Zhongze Z Xie Zhuoying Z Li Yan Y Guo Xuejiang X

Nature communications 20250816 1

Extracellular vesicles (EVs) carry complex glycoproteins critical mediators of disease progression and hold great potential for liquid biopsy applications. However, their low abundance presents significant analytical challenges. This study develop a versatile platform for EV N-glycoproteomic analysis (EVGpro), which enables tandem EV capture, EV protein digestion, and enrichment of N-glycopeptides. Functionalized magnetic nanochains with cell-penetrating peptides (octa-arginine, R<sub>8</sub>) e ...[more]

PMID: 40819088

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Project description:Background: Cardiovascular disease (CVD) causes more than 50% of deaths in patients with advanced chronic kidney disease (CKD). CVD degree correlates with CKD severity. Clinical studies suggest that kidney-derived factors contribute to the development of CVD in CKD, independently of co-morbidities like hypertension and hyperglycemia. However, to date, no kidney-specific humoral risk factor that triggers direct cardiotoxicity has yet been identified, primarily due to the paucity of studies in patients with reno-cardiac disease. Here, we investigate how, in CKD patients, circulating extracellular vesicles (EVs) facilitate pathological kidney-heart communication, thereby causing cardiotoxicity, impairing cardiac function and contributing to heart failure (HF) progression. Methods and results: EVs isolated from the plasma of patients with CKD (hCKD-EVs), but not healthy controls (hCtr-EVs), were cardiotoxic, significantly inducing apoptosis both in vitro and in vivo and impairing contractility of isolated adult rat primary CMs in vitro. Likewise, EVs isolated from both plasma and kidneys of adenine diet-induced CKD mice were also cardiotoxic. Pharmacologically depleting circulating EVs in CKD mice significantly recovered cardiac function and ameliorated HF, suggesting CKD-EVs play a causal role in HF pathogenesis. Small RNA sequencing and q-RT-PCR validation uncovered distinct miRNAs enriched in both human and mouse CKD-EVs, compared to Ctr-EVs. CKD-EV-miRNA mimics were cardiotoxic to human ventricular AC16 myocytes inducing apoptosis and to iPSC-derived cardiomyocytes, impairing contractility and downregulating contractile gene expression. Interestingly, levels of endogenous primary miRNAs corresponding to CKD-EV-miRNAs were significantly higher in CKD-kidney tissues, specifically in CD45-veCD31-ve renal cells, but not in CKD-livers, CKD-lungs or CKD-PBMCs from peripheral blood, a result that suggests that CKD-EV-miRNAs originate renally. Remarkably, CKD-EV-miRNA levels correlated with established markers of cardiac injury, uncovering the presence of sub-clinical heart disease and demonstrating heterogeneity in CKD patients not yet diagnosed with HF. Conclusion: Collectively, our human subject and mouse studies show that circulating CKD-EVs, carrying distinct renal-derived miRNAs, mediate the molecular crosstalk that contributes to the pathogenesis of HF in CKD. Consequently, CKD-EVs hold promise as diagnostic and prognostic biomarkers for early disease detection and as targets for novel therapeutic interventions in chronic reno-cardiac disease.

Dataset Information

Tandem proteomic and N-glycoproteomic analysis of extracellular vesicles

Publications

A functionally tunable magnetic nanochains platform for N-glycoproteomic analysis of extracellular vesicles from ultratrace biofluids.

Similar Datasets

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