Hereditary cerebral small vessel disease : insights from matrisome

Abstract

The cerebral small vessel disease (CSVD) is a pathological condition commonly observed in elderly population and causes cognitive impairment and gait disturbance. Despite the importance of the disease, little is known about its molecular pathogenesis. The discovery of causative genes for hereditary CSVD has opened up new ways of understanding the molecular pathogenesis of CSVD. COL4A1 and COL4A2 for COL4A1/2–related small vessel disease, NOTCH3 for autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and HTRA1 for autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) are the representative. The current topic from recent advances of the hereditary CSVD study is the matrisome, which is a term of the repertoire of extracellular matrix (ECM) proteins. ECM proteins fill the extracellular space and create tissue–specific microenvironment cooperatively. Most of the hereditary CSVD involves the matrisome in small vessels, suggesting that the tissue–specific microenvironment is not harmonious. Here we discuss the molecular mechanisms of the hereditary CSVD in terms of the disturbance of the matrisome. The concept helps us understand the CSVD pathogenesis.