Haffner Christof, Malik Rainer, Dichgans Martin
J Cereb Blood Flow Metab. 2016 Jan;36(1):158-71. doi: 10.1038/jcbfm.2015.71.
Cerebral small vessel disease (SVD) is among the most frequent causes of both stroke and dementia. There is a growing list of genes known to be implicated in Mendelian forms of SVD. Also, genome-wide association studies have identified common variants at a number of genetic loci that are associated with manifestations of SVD, among them loci for white matter hyperintensities, small vessel stroke, and deep intracerebral hemorrhage. Driven by these discoveries and new animal models substantial progress has been made in elucidating the molecular, cellular, and physiologic mechanisms underlying SVD. A major theme emerging from these studies is the extracellular matrix (ECM). Recent findings include a role of structural constituents of the ECM such as type IV collagens in hereditary and sporadic SVD, the sequestration of proteins with a known role in ECM maintenance into aggregates of NOTCH3, and altered signaling through molecules known to interact with the ECM. Here, we review recent progress in the identification of genes involved in SVD and discuss mechanistic concepts with a particular focus on the ECM.
脑小血管病（SVD）是中风和痴呆最常见的病因之一。已知有越来越多的基因与孟德尔形式的SVD有关。此外，全基因组关联研究已经在多个基因位点鉴定出常见变异，这些变异与SVD的表现相关，其中包括与白质高信号、小血管中风和深部脑出血相关的基因位点。在这些发现和新动物模型的推动下，在阐明SVD潜在的分子、细胞和生理机制方面取得了重大进展。这些研究中出现的一个主要主题是细胞外基质（ECM）。最近的发现包括ECM的结构成分如IV型胶原蛋白在遗传性和散发性SVD中的作用、在ECM维持中起已知作用的蛋白质被隔离到NOTCH3聚集体中，以及通过已知与ECM相互作用的分子改变信号传导。在此，我们综述了在鉴定与SVD相关基因方面的最新进展，并特别关注ECM来讨论机制概念。
