Serum extracellular vesicle protein levels are associated with acute coronary syndrome

Abstract

Aims: Biomarkers are essential in the early detection of acute coronary syndromes (ACS). Serum extracellular vesicles are small vesicles in the plasma containing protein and RNA and have been shown to be involved in ACS-related processes like apoptosis and coagulation. Therefore, we hypothesized that serum extracellular vesicle protein levels are associated with ACS. Methods and results: Three serum extracellular vesicle proteins potentially associated with ACS were identified with differential Q-proteomics and were evaluated in 471 frozen serum samples of ACS-suspected patients presenting to the emergency department (30% of whom had an ACS). Protein levels were measured after vesicle isolation using ExoQuick. Mean serum extracellular vesicle concentration of the different proteins was compared between ACS and non-ACS patients. Selected proteins were tested in a univariate logistic regression model, as well as in a multivariate model to adjust for cardiovascular risk factors. A separate analysis was performed in men and women. In the multivariate logistic regression analysis, polygenic immunoglobulin receptor, (pIgR; OR 1.630, p=0.026), cystatin C (OR 1.641, p=0.021), and complement factor C5a (C5a, OR 1.495, p=0.025) were significantly associated with ACS, while total vesicle protein concentration was borderline significant. The association of the individual proteins with ACS was markedly stronger in men. Conclusions: These data show that serum extracellular vesicle pIgR, cystatin C, and C5a concentrations are independently associated with ACS and that there are pronounced gender differences. These observations should be validated in a large, prospective study to assess the potential role of vesicle content in the evaluation of patients suspected of having an ACS.

Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex

“…Spermatozoa were pelleted by centrifugation for 10 min at 1000 × g at 4°C. Seminal plasma or blood serum samples were stored at −80°C until purification of exosomes using ExoQuick (SBI) exosome precipitation reagent as previously described (de Hoog et al, 2013; Madison et al, 2014; Quackenbush et al, 2014; Rekker et al, 2013) or sucrose gradient differential ultracentrifugation (Madison et al, 2014). Supernatant (exosome depleted seminal plasma or blood serum) was discarded, the SE or BE exosome pellet was washed in PBS three times for 30 minutes at 4°C and 100,000 × g , resuspended in PBS vehicle, aliquoted, quantified by the Bradford method and stored at −80°C until use.…”

Plasma extracellular vesicle protein content for diagnosis and prognosis of global cardiovascular disease

“…Extracellular vesicle protein levels, however, have only recently been described to carry information in the presence of ACS [15]. Following a proteomics discovery approach, we demonstrated in a chest pain cohort of 471 patients that pIgR, Cystatin C (CST3), C5a and total vesicle protein concentration are associated with the presence of ACS.…”

“…Although relatively unexplored due to technical challenges, vesicle proteins hold promise as mass spectrometry-based proteomic technology is rapidly emerging for identification and quantification of extremely low abundant proteins in a sample. This has already resulted in identification of vesicle proteins for the diagnosis of ACS [15] and prognosis of secondary cardiovascular events [17] in clinical cohorts. Isolation of plasma extracellular vesicle subpopulations is expected to lead to new and better cardiovascular vesicle protein biomarkers in a new sample set.…”

Role of C5a-C5aR axis in the development of atherosclerosis

“…The relationship between plasma levels of C5a and cardiovascular risk has been investigated. In a study of 471 patients, serum C5a level was found significantly associated with acute coronary syndrome [32]. As well, elevated C5a level may be associated with increased cardiovascular risk (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death) in patients with advanced atherosclerosis after a median follow-up of 22 months [20].…”