Dorschel Kirsten B, Wanebo John E
Medical Faculty, Heidelberg University Medical School, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.
Front Neurol. 2023 May 16;14:661611. doi: 10.3389/fneur.2023.661611. eCollection 2023.
The 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.
This 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.
References 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.
MMA 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.
烟雾病（MMA）的病因及病理生理机制仍 largely 未知。MMA 是一种进行性闭塞性脑血管疾病，其特征为反复发生缺血性和出血性中风；伴有代偿性形成异常的穿支血管网络以建立侧支循环；以及在脑底部出现异常血管生成。血管生成和血管发生机制的失衡被认为是 MMA 的一个潜在病因。烟雾血管提示异常的血管生成、动脉生成和血管发生过程可能参与了 MMA 的病理生理过程。循环内皮祖细胞被推测有助于 MMA 中的血管重塑。MMA 与血管生成因子和促炎分子的表达增加有关。全身炎症可能与 MMA 的发病机制有关。
本文献综述描述了与 MMA 及相关脑血管疾病中的脑血管功能障碍、异常血管生成和炎症相关的分子机制，以及治疗策略和未来研究前景。
通过使用 PubMed、EMBASE、BIOSIS Previews、CNKI、ISI 科学网和 Medline 数据库，对 1983 年 1 月 1 日至 2022 年 7 月 29 日的医学文献进行系统的计算机检索，并使用关键词“烟雾病”“血管生成”“吻合网络”“分子机制”“生理学”“病理生理学”“发病机制”“生物标志物”“遗传学”“信号通路”“血脑屏障”“内皮祖细胞”“内皮功能”“炎症”“颅内出血”和“中风”的各种组合来识别参考文献。纳入了几乎全部以英文发表的相关文章和补充基础科学文章。通过查阅相关出版物的参考文献列表以获取更多来源，得到了 350 篇符合研究纳入标准的出版物。对 MMA 患者生长因子、趋化因子和细胞因子的检测提示异常血管生成参与 MMA 发病机制的假说。这些发现是 MMA 的后果还是 MMA 的病因因素仍有待确定。
MMA 是一种异质性疾病，包括各种基因型和表型，具有复杂的病理生理学。更多研究可能会增进我们对异常血管生成、动脉狭窄以及烟雾病侧支循环和吻合网络形成所涉及的病理生理学的理解。未来的研究将受益于对分子病理生理机制以及临床和基础研究结果相关性的研究。
