Matrix as an Interstitial Transport System

The extracellular matrix (ECM) is best known for its function as a structural scaffold for the tissue and more recently as a microenvironment to sequester growth factors and cytokines allowing for rapid and localized changes in their activity in the absence of new protein synthesis. In this review, we explore this and additional new aspects of ECM function in mediating cell-to-cell communications. Fibrillar and nonfibrillar components of ECM can limit and facilitate the transport of molecules through the extracellular space while also regulating interstitial hydrostatic pressure. In turn, transmembrane communications via molecules, such as ECM metalloproteinase inducer, thrombospondins, and integrins, can further mediate cell response to extracellular cues and affect ECM composition and tissue remodeling. Other means of cell-to-cell communication include extracellular microRNA transport and its contribution to gene expression in target cells and the nanotube formation between distant cells, which has recently emerged as a novel conduit for intercellular organelle sharing thereby influencing cell survival and function. The information summarized and discussed here are not limited to the cardiovascular ECM but encompass ECM in general with specific references to the cardiovascular system