Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?

Abstract

The term matrisome refers to the ensemble of proteins constituting the extracellular matrix (ECM) (core matrisome) as well as the proteins associated with the ECM. Every organ has an ECM with a unique composition that not only provides the support and anchorage for cells, but also controls fundamental cellular processes as diverse as differentiation, survival, proliferation, and polarity. The current knowledge of the matrisome of small brain vessels is reviewed with a focus on the basement membrane (BM), a specialized form of ECM located at the interface between endothelial cells, contractile cells (smooth muscle cells and pericytes), and astrocyte endfeet—a very strategic location in the communication pathway between the cerebral microcirculation and astrocytes. We discuss some of the most recent genetic data and relevant findings from experimental models of nonamyloid cerebral small vessel disease (SVD). We propose the concept that perturbations of the cerebrovascular matrisome is a convergent pathologic pathway in monogenic forms of SVD, and is likely relevant to the sporadic disease.