Fibronectin: structure, assembly, and cardiovascular implications.

In the past 2 decades, it has been appreciated that the functions of the extracellular matrix (ECM) are not entirely structural. ECM components interact with specific adhesion receptors on cell surfaces and regulate various cellular functions, including differentiation, proliferation, migration, and apoptosis. Fibronectin (FN) is a paradigm adhesive protein, nonreactive with adhesion receptors in its soluble state but highly adhesive when insoluble. Polymerization of FN into the ECM must be tightly regulated to ensure that the adhesive information in the ECM is appropriate. FN exists in a soluble protomeric form in micromolar concentration in blood plasma and in an insoluble multimeric form in the ECM. Unlike fibrillar or basement membrane collagens, laminins, actin, and tubulin, circulating FN does not self-polymerize in physiologically relevant solutions. Furthermore, there is little passive accumulation of FN in preexisting ECM. Rather, assembly of FN takes place at specialized areas on the cell surface. FN is especially abundant in the ECM of embryonic and regenerating or injured tissues, although it can be found in most ECMs, including basement membranes. FN interacts with cells through integrins, heterodimeric transmembrane receptors linking the ECM to the intracellular cytoskeleton and signaling pathways. The aim of this review is to describe the mechanisms and consequences of FN deposition and give a brief overview of the significance of FN for selected areas of cardiovascular research. In the first section we describe important features of the FN molecule that account for its multiple functions. Next, we focus on the assembly process, ie, the conversion of soluble FN to its active, adhesive, insoluble form. Finally, we discuss several areas of cardiovascular research in which FN may have an important role, exemplifying how the adhesive information of FN can drive pathophysiological processes.