Plasma extracellular vesicle proteins are associated with stress-induced myocardial ischemia in women presenting with chest pain

Abstract

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. Currently, no blood test is available. Plasma extracellular vesicles (EV) are emerging as potential biomarker source. We therefore aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. We analyzed 450 patients suspected for stable IHD who were referred for 82 Rb PET/CT in the outpatient clinic. Blood samples were collected before PET/CT and plasma EVs were isolated in 3 plasma subfractions named: TEX, HDL, LDL. In total 6 proteins were quantified in each of these subfractions using immuno-bead assays. CD14 and CystatinC protein levels were independent significant predictors of stress-induced ischemia in the LDL and the HDL subfraction and SerpinC1 and SerpinG1 protein levels in the HDL fraction. Subgroup-analysis on sex revealed that these associations were completely attributed to the associations in women. None of the significant EV proteins remained significant in men. Plasma EV proteins levels are associated with the presence of stable IHD in females presenting with chest pain. This finding, if confirmed in larger cohort studies could be a crucial step in improving diagnostic assessment of women with suspected IHD.

Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels in chronic coronary disease: A LoDoCo2 biomarker substudy

“…Iodixanol density gradient centrifugation of the subfraction was used to determine in which density fraction NLRP3 protein was present in the TEX fraction. Characterization of the density fractions of TEX isolation was described in detail before [21,22]. In these previous studies, we show that with the precipitation method we used, after density gradient centrifugation there was CD9 positivity (Western blot) in the 1,05-1,09 density.…”

“…Serum EV or cell culture medium EV subfractions were isolated using a standardized protocol [21,22].…”

Extracellular Vesicles in Diagnosing Chronic Coronary Syndromes the Bumpy Road to Clinical Implementation

“…The myomarker study cohort consisted of consecutive patients presenting with stable chest pain at the outpatient clinic of the Meander Medical Centre in the Netherlands. Details on the study design and study population can be found in a previous publication [108]. For this study, a case control analysis of 44 men suspected of CCS was performed.…”

“…For EV-based diagnosis of CCS, not many data exist. A recent study investigated whether a selected group of EV-proteins were associated with CCS [108]. EV-Serpin C1, EV-CD14, EV-Serpin G1, EV-Serpin F2 and EV-Cystatin C (mostly in the HDL-subpopulation) were shown to be independently associated with the presence of stress-induced ischemia.…”

“…A large study investigating biomarkers within CVD showed a difference in protein profile between men and women of almost 85% [120]. Research performed in EVs also showed differences in the associations of both EV count as well as content with clinical outcomes stratified on clinical factors [103,108,112].…”