Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells.

Francesca Tinelli,Francesco Arioli,Vincenzo Di Lazzaro,Daniela Lisini,Giuseppe Faragò,Alessandro Pezzini,Federica Zibordi,Veronica Saletti,Nardo Nardocci,Ignazio G Vetrano,Francesco Acerbi,Paolo Ferroli,Laura Gatti,Peter Vajkoczy,Chiara Pantaleoni,Fioravante Capone,Andrea Gioppo,Gloria Bedini,Sara Nava,Esposito Susan ,Bradford B Worrall ,Emma Scelzo ,Maria Luisa Dell’acqua ,Elisabeth Tournier‐Lasserve ,Eugenio Parati ,Elisa Ciceri ,Marialuisa Zedde

doi:10.3390/ijms21165763

Abstract

The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

Highlights

Moyamoya angiopathy (MA) is a rare, chronic, and disabling cerebrovascular disease with a prevalence of 0.086–10.5/100,000
Reduced levels of Circulating endothelial progenitor cells (cEPCs) have been shown to be related to endothelial dysfunction, cerebral infarction, and coronary artery disease, which suggests that endothelial progenitor cell (EPC) play an important role in vascular homeostasis [35,36,37,38]
It was suggested that reduced numbers and impaired functions of cEPCs are related to the pathogenesis of stroke [39,40]

Summary

Introduction

Moyamoya angiopathy (MA) is a rare, chronic, and disabling cerebrovascular disease with a prevalence of 0.086–10.5/100,000 It is characterized by a progressive steno-occlusive lesion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the compensatory development of an unstable network of collateral vessels at the base of the brain (Moyamoya vessels) [1,2]. These vascular hallmarks are responsible for recurrent ischemic and hemorrhagic strokes (about 80% of cases), leading children and adults affected by MA to severe neurological (sensorimotor, speech, and cognitive) deficits, progressive physical disabilities, and even death [3,4]. It is believed that MA results from a complex mechanism in which acquired infectious, inflammatory, and flow dynamic conditions may trigger the disease in genetic susceptible individuals through angiogenic and vasculogenic pathways abnormalities [2]

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