Emerging molecular mechanism for cerebral small vessel disease: Lessons from hereditary small vessel disease

Abstract

AbstractCerebral small vessel disease is a common disorder in the elderly. The findings of hereditary small vessel disease studies clearly show that small vessel diseases have a distinct molecular pathway that is different from that in large vessels. However, the anatomical and functional heterogeneity of the cerebral small vessel system makes it difficult to understand the concept and molecular mechanism for small vessel disease. The purpose of this review is to explain the heterogeneity of small vessels and the importance of the components of the capillary system in the pathogenesis of cerebral small vessel disease. Although traditional investigations have focused more attention on the arteriole, the most functional part of small arteries is the capillary. Therefore, the capillary might play an important role in the pathogenesis of small vessel disease. In the capillary, pericytes and astrocytes are unique components with marked diversity. However, the molecular signature and function of pericytes remain unknown. Furthermore, the morphology and molecular signature of astrocytes in the cortex and white matter are quite different. Therefore, the mechanism of small vessel disease is not simple, and must be investigated considering the diversities of small vessels. In the capillary, cross‐talk between cell components exists. Among these cell signaling pathways, recent findings on the gene responsible for hereditary small vessel disease show that transforming growth factor‐β and platelet‐derived growth factor‐β could contribute to the molecular pathogenesis of small vessel disease. These findings provide useful information for the development of a new therapeutic strategy for small vessel disease.