Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke

Abstract

Introduction: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS).

Materials and methods: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs.

Results: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed.

Conclusion: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

Keywords: Atherosclerosis; Carotid plaques; Intima-media thickness; Ischemic stroke; Platelet-derived microvesicles; Recurrent vascular event.