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

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.

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

“…The stenotic changes seen in MA are not characterized by lipid pools, inflammatory cells, or macrophage invasion to the sub-intimal layer, as typically seen in atherosclerosis [8]. Due to the detection of altered levels of endothelial progenitor cells (EPC), cytokines, chemokines, and growth factors in MA patient biological fluids, impaired angiogenesis and vasculogenesis have been invoked as potential disease mechanisms [2,9,19].…”

The Genetic Basis of Moyamoya Disease

“…As mentioned above, MMD is mainly characterized by progressive spontaneous bilateral occlusion of the terminal ICA and their major branches with compensatory capillary collaterals as an expression of pathologically increased angiogenic activity [3]. Histological examinations of the stenoocclusive arteries revealed fibrocellular thickening of the intima caused by proliferation of smooth muscle cells (SMC) with abnormal findings such as irregular undulation of the internal elastic lamina and significantly thinner media with absence of atheromatous plaques [33][34][35].…”

“…Moyamoya disease (MMD), first described in 1957 by Takeuchi and Shimizu [1] and characterized as a new disease entity in 1969 by Suzuki and Takaku [2], is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal carotid arteries (ICA) and their major branches (middle cerebral artery, MCA, and anterior cerebral artery, ACA) with compensatory capillary collaterals as an expression of pathologically increased angiogenic activity [3] resembling a "puff of smoke" (Japanese: Moyamoya) on cerebral angiography. Moyamoya collaterals may disappear with development of meningeal collaterals from the external cerebral arteries (ECA).…”

Characteristics of Moyamoya Disease in the Older Population: Is It Possible to Define a Typical Presentation and Optimal Therapeutical Management?

“…The pathogenesis of idiopathic MA is unknown. Anomalies in angiogenesis, due to the detection of increased cytokine and growth factor concentrations have been invoked as potential disease mechanisms [ 3 ]. Given the familial rate, especially in the Eastern countries, and the ethnic differences, genetic factors are also believed to be involved [ 4 , 5 ].…”