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.