Emerging roles of CCN proteins in vascular development and pathology.

The CCN family of proteins consists of 6 members (CCN1-CCN6) that share conserved functional domains. These matricellular proteins interact with growth factors, extracellular matrix (ECM) proteins, cell surface integrins and other receptors to promote ECM-intracellular signaling. This signaling leads to propagation of a variety of cellular actions, including adhesion, invasion, migration and proliferation within several cell types, including epithelial, endothelial and smooth muscle cells. Though CCNs share significant homology, the function of each is unique due to distinct and cell specific expression patterns. Thus, their correct spatial and temporal expressions are critical during embryonic development, wound healing, angiogenesis and fibrosis. Disruption of these patterns leads to severe development disorders and contributes to the pathological progression of cancers, vascular diseases and chronic inflammatory diseases such as colitis, rheumatoid arthritis and atherosclerosis. While the effects of CCNs are diverse, this review will focus on the role of CCNs within the vasculature during development and in vascular diseases.