The Impact of Moyamoya Disease and RNF213 Mutations on the Spectrum of Plasma Protein and MicroRNA.

Ming-Jen Lee,Kai Wang,Shannon Fallen,David Baxter,Kelsey Scherler,Yong Zhou,Meng-Fai Kuo

doi:10.3390/jcm8101648

Abstract

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by occlusion of bilateral internal carotid and intracerebral arteries with the compensatory growth of fragile small vessels. MMD patients develop recurrent infarctions in the basal ganglia and subcortical regions. Symptoms include transient ischemic attack or stroke, seizures, and headaches, which may occur suddenly or in a stepwise progression. Mutations in Ring Finger Protein 213 (RNF213), a Zinc ring finger protein, have been identified in some MMD patients but the etiology of MMD is still largely unknown. To gain insight into the pathophysiology of MMD, we characterized the impact of the RNF213 mutations on plasma protein and RNA profiles. Isobaric tags for relative and absolute quantitation and proximity extension assay were used to characterize the plasma proteome. Next generation sequencing-based small RNAseq was used to analyze the cell-free small RNAs in whole plasma and RNA encapsulated in extracellular vesicles. The changes of miRNAs and proteins identified are associated with signaling processes including angiogenesis and immune activities which may reflect the pathology and progression of MMD.

Highlights

Moyamoya disease (MMD) is a rare disorder first described in 1969 in Japanese patients [1] and the majority of cases are from Eastern Asian descent
8 million raw reads were obtained in whole plasma, extracellular vesicles (EVs) and EV-depleted plasma samples (Table 1)
No significant differences in raw and trimmed read counts were observed between samples from MMD patients and controls

Summary

Introduction

Moyamoya disease (MMD) is a rare disorder first described in 1969 in Japanese patients [1] and the majority of cases are from Eastern Asian descent. MMD is characterized by bilateral stenosis of internal carotid arteries (ICAs) with frequent involvement of anterior and middle cerebral arteries. The stenotic ICAs in MMD patients show thickening of intima, proliferation of smooth muscle cells, and prominently tortuous and duplicated internal elastic lamina [2,3]. To compensate for the occlusion, a large number of tiny and weak vessels are overgrown with the appearance of a “puff of smoke” (termed moyamoya in Japanese) under conventional angiography. Several genetic loci have been linked to MMD and mutations in RNF213 [6,7] and ACTA2 [8] genes have been identified in some patients, but the etiology of disease is still unclear

Methods

Results

Conclusion