Elastin receptor and cell-matrix interactions in heart transplant-associated arteriosclerosis

Vascular cells, as well as monocytes, neutrophils, and lymphocytes which may infiltrate vascular walls and tissues express a multifunctional 67 kD protein which also serves as a subunit of the cell surface "elastin receptor". This protein differs structurally and functionally from other matrix adhesion molecules. Unlike the integrins or cadherins, it is not a transmembrane molecule, but can be immobilized on the cell surface by association with two other membrane-anchored proteins. Once expressed on the cell surface, it may mediate cell-matrix interaction in a calcium-independent manner. Unlike most integrins, which recognize the linear sequence on the matrix ligands (RGD), it recognizes the secondary structure of the matrix macromolecules and binds to several non identical domains on different matrix components, as long as they form the appropriate hydrophobic conformation. Similarly to the transmembrane selectins, the 67 kD protein has lectin-like properties with the galactosugars' binding specificity. However, binding of galactosugar-bearing ligands interrupts its contacts with matrix proteins and displaces the 67 kD protein from the cell surface. Moreover, the 67 kD protein also serves as an intracellular chaperone which facilitates secretion of tropoelastin and assembly of elastic fibers. In this review I will address the role of this 67 kD protein in mechanisms of mutual interaction between vascular smooth muscle cells, infiltrating leukocytes, and several components of extracellular matrix during the development of heart-transplant associated arteriosclerosis.