Age-related alterations in the signal transduction pathways of the elastin-laminin receptor

With aging we assist to alterations in the vascular structure and function. One important factor in these vascular wall changes is the degradation of the elastin fibre major protein: elastin. Elastin peptides derived from the degradation are present in human sera. Elastin peptides induce on fibrobla sts, phagocytic cells, lymphocytes, smooth muscle cells and endothelial cel ls, a variety of biological effects mediated by the elastin-laminin recepto r which has been demonstrated to be present on the membrane of these cells. The transduction pathway of the ELR receptor involves the activation of ph ospholipase C (PLC) by a pertussis toxin sensitive G-protein. PLC induces t he production of inositol trisphosphate (IP3) leading to the increase of th e intracellular free calcium on one hand, and of diacylglycerol (DAG) which stimulates the translocation to the membrane of PKC leading to the phospho rylation of members of the MAPK family such as p42/p44 MAPK. A progressive age dependent uncoupling of the elastin-laminin receptor occurs impairing i ts transduction pathway and which results in alteration of the calcium sign aling and loss in calcium homeostasis of the cells. These alterations in th e signal transduction of the elastin-laminin receptor result in modified ac tivities of parenchymal and phagocytic cells with aging, such as free radic al production and elastase release. Thus, these age-related alterations in the elastin-laminin receptor signal transduction may be involved in the ath erogenesis. (C) 2001 Editions scientifiques et medicales Elsevier SAS.