Regulation of vascular cell behavior by collagen : form is function.

Abstract

The vascular extracellular matrix (ECM) is a complex mixture of collagens, elastin, glycoproteins, and proteoglycans. These constituents not only provide mechanical integrity to the vessel wall but comprise a repertoire of insoluble ligands that can signal the cell to control proliferation, migration, differentiation, and survival. In the normal adult artery wall, the basement membrane is the primary ECM compartment that interacts with the vascular smooth muscle cell (SMC), and its components are believed to be important in maintaining a stable and well-differentiated SMC.1 However, during conditions of arterial restructuring, the ECM can be quickly remodeled through a combination of synthesis of new ECM molecules, regulated assembly of these molecules, and proteolytic degradation and editing of existing structures. Together, these actions provide a new and dynamic set of ECM stimuli that can have a profound effect on SMC behavior. One of the most abundant ECM molecules of both healthy and diseased arteries is type I collagen, a fibril-forming, heterotrimeric molecule comprised of two α1(I) collagen chains and one α2(I) collagen chain. These chains are synthesized as soluble propeptides that wind around each other in the endoplasmic reticulum to form type I procollagen, with its long triple helical domain. As type I procollagen molecules are transported to the cell surface, they associate with each other.2 These aggregates nonetheless remain in solution, by virtue of the nonhelical domains of procollagen at the amino and carboxy termini. Outside the cell, the propeptide termini are proteolytically removed, on which collagen molecules fall out of solution and …