Dataset Information

Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD).

ABSTRACT: 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 < 0.05) and associated with increased amputation risk before and after covariate adjustment (mean follow-up 3.6 years, p < 0.01). The combination of calprotectin with hs-CRP in the multivariate analysis further improved risk stratification (p < 0.01). Furthermore, S100A9 was also expressed in femoral plaque derived EVs and tissues. In summary, we found that PAD patients release EVs, mainly of platelet origin, highly positive for AnnexinV and rich in transcripts related to platelet biology and immune responses. Amputation risk prediction improved with calprotectin and was significantly higher when combined with hs-CRP. Our results suggest that EVs can be a promising component of liquid biopsy to identify the molecular signature of PAD patients.

SUBMITTER: Saenz-Pipaon G

PROVIDER: S-EPMC7048174 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD).

Saenz-Pipaon Goren G San Martín Patxi P Planell Núria N Maillo Alberto A Ravassa Susana S Vilas-Zornoza Amaia A Martinez-Aguilar Esther E Rodriguez José Antonio JA Alameda Daniel D Lara-Astiaso David D Prosper Felipe F Paramo José Antonio JA Orbe Josune J Gomez-Cabrero David D Roncal Carmen C

Journal of extracellular vesicles 20200219 1

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 prospectiv ...[more]

PMID: 32158521

Similar Datasets

Project description:BackgroundThe VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches.Methods and resultsBenefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation.ConclusionsThese analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.

Project description:Background and objectivesWe aimed to investigate the history of medical resource consumption and quality of life (QoL) in peripheral arterial disease (PAD) patients in Korea.MethodsThis was a prospective, multi-center (23 tertiary-hospitals, division of cardiology), non-interventional study. Adult patients (age ?20 years) suffering from PAD for the last 12-month were enrolled in the study if they met with any of following; 1) ankle-brachial index (ABI) ?0.9, 2) lower-extremity artery stenosis on computed tomography angiography ?50%, or 3) peak-systolic-velocity-ratio (PSVR) on ultrasound ?2.0. Medical chart review was used to assess patient characteristics/treatment patterns while the history of medical resource consumption and QoL data were collected using a patient survey. QoL was measured using EuroQoL-5-dimensions-3-level (EQ-5D-3L) score system, and the factors associated with QoL were analyzed using multiple linear regression analysis.ResultsThis study included 1,260 patients (age: 69.8 years, male: 77.0%). The most prevalent comorbidities were hypertension (74.8%), hyperlipidemia (51.0%) and diabetes-mellitus (50.2%). The 94.1% of the patients took pharmacotherapy including aspirin (76.2%), clopidogrel (53.3%), and cilostazol (33.6%). The 12.6% of the patients were receiving smoking cessation education/pharmacotherapy. A considerable number of patients (500 patients, 40.0%) had visit history to another hospital before diagnosis/treatment at the current hospital, with visits to orthopedic units (50.4%) being the most common. At the time, 29% (or higher) of the patients were already experiencing symptoms of critical limb ischemia. Baseline EQ-5D index and EQ VAS were 0.64±0.24 and 67.49±18.29. Factors significantly associated with QoL were pharmacotherapy (B=0.05053; p=0.044) compared to no pharmacotherapy, and Fontaine stage improvement/maintain stage I (B=0.04448; p<0.001) compared to deterioration/maintain stage II-IV.ConclusionsIncrease in disease awareness for earlier diagnosis and provision of adequate pharmacotherapy is essential to reduce disease burden and improve QoL of Korean PAD patients.

Dataset Information

Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD).

Publications

Functional and transcriptomic analysis of extracellular vesicles identifies calprotectin as a new prognostic marker in peripheral arterial disease (PAD).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets