Abstract
High levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of patients with cardiovascular disease. The PROFLOW study consists of 220 patients with prior myocardial infarction and measured CFR with transthoracic echocardiography. The patients were divided into high and low CFR groups. Plasma MVs were captured with acoustic trapping. Platelet- and endothelial-derived MVs were measured with flow cytometry, and vesicle lysates were analyzed with proteomic panels against cardiovascular biomarkers. Flow cytometry was further applied to identify cellular origin of biomarkers. Our data show a negative correlation between MV concentration and CFR values. Platelet and endothelial MV levels were significantly increased in plasma from the low CFR group. CFR negatively correlates with the levels of several proteomic biomarkers, and the low CFR group exhibited higher concentrations of these proteins in MVs. Focused analysis of one of the MV proteins, B cell activating factor (BAFF), revealed platelet and not leukocyte origin and release upon proinflammatory stimulus. Higher levels of MVs carrying an elevated concentration of proatherogenic proteins circulate in plasma in patients with low CFR, a marker of vascular dysfunction, reduced blood flow, and poor prognosis. Our findings demonstrate a potential clinical value of MVs as biomarkers and possible therapeutic targets against endothelial deterioration.NEW & NOTEWORTHY We investigated how microvesicles (MVs) from patients with cardiovascular diseases are related to coronary flow reserve (CFR), a clinical parameter reflecting blood flow in the heart. Our results show a negative relationship between CFR and levels of platelet and endothelial MVs. The pattern of MV-enriched cardiovascular biomarkers differs between patients with high and low CFR. Our findings suggest a potential clinical value of MVs as biomarkers of reduced blood flow and proatherogenic status, additional to CFR.
Highlights
NEW & NOTEWORTHY We investigated how microvesicles (MVs) from patients with cardiovascular diseases are related to coronary flow reserve (CFR), a clinical parameter reflecting blood flow in the heart
Endothelial dysfunction is a known contributor to atherosclerosis and development of coronary artery disease (CAD)
It was shown that MVs generated from activated endothelial cells enhance platelet aggregation ex vivo through a von Willebrand factor-dependent mechanism of crosslinking [9] and contribute to the development of atherosclerosis through, e.g., enhancing clotting cascade, interacting with monocytes, and facilitating EC proliferation [10]
Summary
Endothelial dysfunction is a known contributor to atherosclerosis and development of coronary artery disease (CAD). It was shown that MVs generated from activated endothelial cells enhance platelet aggregation ex vivo through a von Willebrand factor (vWF)-dependent mechanism of crosslinking [9] and contribute to the development of atherosclerosis through, e.g., enhancing clotting cascade, interacting with monocytes, and facilitating EC proliferation [10]. They can modulate vascular smooth muscle cell differentiation and plaque progression [11].
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