Cellular interactions in vascular growth and differentiation.

In nature, mammalian cells do not exist in isolation, but rather are involved in interactions with other cells and matrix. In this review, several aspects of cellular interactions that are important in vascular growth and development will be highlighted. The cardiovascular system is the earliest to develop in the embryo. A number of growth factors and their receptors mediate the complex stages of migration, assembly, organization, and stabilization of developing vessels. In the adult organism, normal angiogenesis is restricted primarily to tissue growth (such as muscle and fat), the wound healing process and the female reproductive system. However, pathological angiogenesis, such as with tumor growth, diabetic retinopathy, and arthritis, is of great concern. The identification and/or development of exogenous and endogenous angiogenesis inhibitors has added to the understanding of these pathological processes. In addition to cellular interactions via ligands and receptors, cells also interact directly through physical contacts. These interactions facilitate anchorage, communication, and permeability. Since vessels serve as non-leaky conduits for blood flow as well as interfaces for molecular diffusion, the physical interactions between the cells that make up vessels must be specific for the function at hand. Permeability is a specialized function of vessels and is mediated by intracellular mechanisms and intercellular interactions. Cells also interact with the surrounding extracellular matrix. Integrin-matrix interaction is a two-way exchange critical for angiogenesis. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases play major roles in embryonic remodeling, adult injury, and pathological conditions. Several experimental model systems have been useful in our understanding of cellular interactions. These in vitro models incorporate heterotypic cell-cell interactions and/or allow cell-matrix interactions to occur.