Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD)
Autor: | Goren Saenz-Pipaon, Patxi San Martín, Núria Planell, Alberto Maillo, Susana Ravassa, Amaia Vilas-Zornoza, Esther Martinez-Aguilar, José Antonio Rodriguez, Daniel Alameda, David Lara-Astiaso, Felipe Prosper, José Antonio Paramo, Josune Orbe, David Gomez-Cabrero, Carmen Roncal |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | Journal of Extracellular Vesicles, Vol 9, Iss 1 (2020) |
Druh dokumentu: | article |
ISSN: | 2001-3078 20013078 |
DOI: | 10.1080/20013078.2020.1729646 |
Popis: | Peripheral arterial disease (PAD) is associated with a high risk of cardiovascular events and death and is postulated to be a critical socioeconomic cost in the future. Extracellular vesicles (EVs) have emerged as potential candidates for new biomarker discovery related to their protein and nucleic acid cargo. In search of new prognostic and therapeutic targets in PAD, we determined the prothrombotic activity, the cellular origin and the transcriptomic profile of circulating EVs. This prospective study included control and PAD patients. Coagulation time (Procoag-PPL kit), EVs cellular origin and phosphatidylserine exposure were determined by flow cytometry in platelet-free plasma (n = 45 PAD). Transcriptomic profiles of medium/large EVs were generated using the MARS-Seq RNA-Seq protocol (n = 12/group). The serum concentration of the differentially expressed gene S100A9, in serum calprotectin (S100A8/A9), was validated by ELISA in control (n = 100) and PAD patients (n = 317). S100A9 was also determined in EVs and tissues of human atherosclerotic plaques (n = 3). Circulating EVs of PAD patients were mainly of platelet origin, predominantly Annexin V positive and were associated with the procoagulant activity of platelet-free plasma. Transcriptomic analysis of EVs identified 15 differentially expressed genes. Among them, serum calprotectin was elevated in PAD patients (p |
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