Genetic and Proteomic Contributions to the Pathophysiology of Moyamoya Angiopathy and Related Vascular Diseases

Abstract

Rationale

This literature review describes the pathophysiological mechanisms of the current classes of proteins, cells, genes, and signaling pathways relevant to moyamoya angiopathy (MA), along with future research directions and implementation of current knowledge in clinical practice.

Objective

This article is intended for physicians diagnosing, treating, and researching MA.

Methods and Results

References were identified using a PubMed/Medline systematic computerized search of the medical literature from January 1, 1957, through August 4, 2020, conducted by the authors, using the key words and various combinations of the key words “moyamoya disease,” “moyamoya syndrome,” “biomarker,” “proteome,” “genetics,” “stroke,” “angiogenesis,” “cerebral arteriopathy,” “pathophysiology,” and “etiology.” Relevant articles and supplemental basic science articles published in English were included. Intimal hyperplasia, medial thinning, irregular elastic lamina, and creation of moyamoya vessels are the end pathologies of many distinct molecular and genetic processes. Currently, 8 primary classes of proteins are implicated in the pathophysiology of MA: gene-mutation products, enzymes, growth factors, transcription factors, adhesion molecules, inflammatory/coagulation peptides, immune-related factors, and novel biomarker candidate proteins. We anticipate that this article will need to be updated in 5 years.

Conclusion

It is increasingly apparent that MA encompasses a variety of distinct pathophysiologic conditions. Continued research into biomarkers, genetics, and signaling pathways associated with MA will improve and refine our understanding of moyamoya’s complex pathophysiology. Future efforts will benefit from multicenter studies, family-based analyses, comparative trials, and close collaboration between the clinical setting and laboratory research.

Keywords:

• genetics
• moyamoya
• pathophysiology
• proteomics
• stroke

Ethics

To the best of our knowledge, this manuscript meets all updated current ethics statements.

Acknowledgments

The authors thank Samantha Soto, Rogena Lake, and Laura Repak for manuscript preparation; Mary Ann Clifft, Paula Higginson, and Lynda Orescanin for editing; Cassandra Todd, Cindy Giljames, and Kristen Larson for illustrations; all in Neuroscience Publications at Barrow Neurological Institute; and Nicole Galvan at St. Joseph’s Hospital and Medical Center for help with the literature search.

Disclosure

The authors report no potential conflict of interest relevant to this article.

Additional information

Funding

The authors have not received a fee from any organization to write this review.