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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.

SUBMITTER: Dorschel KB

PROVIDER: S-EPMC7987310 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RationaleThe etiology and pathophysiological mechanisms of moyamoya angiopathy (MMA) remain largely unknown. MMA is a progressive, occlusive cerebrovascular disorder characterized by recurrent ischemic and hemorrhagic strokes; with compensatory formation of an abnormal network of perforating blood vessels that creates a collateral circulation; and by aberrant angiogenesis at the base of the brain. Imbalance of angiogenic and vasculogenic mechanisms has been proposed as a potential cause of MMA. Moyamoya vessels suggest that aberrant angiogenic, arteriogenic, and vasculogenic processes may be involved in the pathophysiology of MMA. Circulating endothelial progenitor cells have been hypothesized to contribute to vascular remodeling in MMA. MMA is associated with increased expression of angiogenic factors and proinflammatory molecules. Systemic inflammation may be related to MMA pathogenesis.ObjectiveThis literature review describes the molecular mechanisms associated with cerebrovascular dysfunction, aberrant angiogenesis, and inflammation in MMA and related cerebrovascular diseases along with treatment strategies and future research perspectives.Methods and resultsReferences were identified through a systematic computerized search of the medical literature from January 1, 1983, through July 29, 2022, using the PubMed, EMBASE, BIOSIS Previews, CNKI, ISI web of science, and Medline databases and various combinations of the keywords "moyamoya," "angiogenesis," "anastomotic network," "molecular mechanism," "physiology," "pathophysiology," "pathogenesis," "biomarker," "genetics," "signaling pathway," "blood-brain barrier," "endothelial progenitor cells," "endothelial function," "inflammation," "intracranial hemorrhage," and "stroke." Relevant articles and supplemental basic science articles almost exclusively published in English were included. Review of the reference lists of relevant publications for additional sources resulted in 350 publications which met the study inclusion criteria. Detection of growth factors, chemokines, and cytokines in MMA patients suggests the hypothesis of aberrant angiogenesis being involved in MMA pathogenesis. It remains to be ascertained whether these findings are consequences of MMA or are etiological factors of MMA.ConclusionsMMA is a heterogeneous disorder, comprising various genotypes and phenotypes, with a complex pathophysiology. Additional research may advance our understanding of the pathophysiology involved in aberrant angiogenesis, arterial stenosis, and the formation of moyamoya collaterals and anastomotic networks. Future research will benefit from researching molecular pathophysiologic mechanisms and the correlation of clinical and basic research results.

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