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Query: UMLS:C0004153 (
atherosclerosis
)
77,401
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Regulation of alphavbeta3 and alpha5beta1 integrin function plays a crucial role in
atherosclerosis
. Possible regulators of integrin-matrix interactions are integrin-binding ADAMs (proteins with a disintegrin- and metalloproteinase-domain), like
ADAM-15
and ADAM-9. Molecular interactions between
ADAM-15
, alpha5beta1, and alphavbeta3 have been demonstrated. ADAM-9 and
ADAM-15
were found to be interdependently regulated. This study, therefore, investigated whether the upregulation of integrins alpha5beta1 and alphavbeta3 was correlated with the expression of integrin-binding ADAMs in atherosclerotic processes. Human arterial and venous vascular smooth muscle cells (VSMCs) were incubated with PDGF over different time intervals up to a 3-day culture period. mRNA concentrations, quantified by real-time RT-PCR and normalized to PBGD, of integrins alphavbeta3 and alpha5beta1 were strongly increased after a 12-h PDGF-incubation in arterial and venous VSMC.
ADAM-15
and ADAM-9 mRNA production showed a corresponding increase following integrin upregulation after a 24-h incubation period. Western blot anaylsis revealed an increased protein expression of integrins and ADAMs in PDGF-stimulated VSMC. Additionally, mRNA concentrations of atherosclerotic and normal human specimens were quantified by real-time RT-PCR. mRNA of ADAMs and integrins was significantly increased in atherosclerotic arteries compared to normal arteries. Immunohistochemistry of these specimens showed an increased expression and codistribution of both ADAMs and integrins in
atherosclerosis
. In conclusion, upregulation of
ADAM-15
and ADAM-9 in
atherosclerosis
appears to follow an increase in alpha5beta1 and alphavbeta3 integrins. Since alpha5beta1 and alphavbeta3 are known to promote smooth muscle cell migration and proliferation, upregulation of
ADAM-15
and ADAM-9 could balance integrin-matrix interactions and cell migration, thus modulating neointima progression.
...
PMID:Increased expression of disintegrin-metalloproteinases ADAM-15 and ADAM-9 following upregulation of integrins alpha5beta1 and alphavbeta3 in atherosclerosis. 1285 46
Cell-cell and cell-matrix interactions are of utmost importance in the pathogenesis of inflammatory diseases. For example, cell-cell and cell-matrix interactions are crucial for leukocyte homing and recruitment to inflammatory sites. The discovery of the disintegrin and metalloprotease (ADAM) proteins, which have both adhesive and proteolytic activities, raised the question of their involvement in inflammatory processes. More interestingly, the presence of the RGD integrin-binding sequence in the disintegrin domain of
ADAM-15
(MDC-15; metargidin) highlighted
ADAM-15
as a protein particularly involved in cell-cell interactions. These findings therefore prompted authors to investigate the roles of
ADAM-15
in inflammatory diseases. Because of the early description of
ADAM-15
expression in endothelial cells, work first focused on the roles of
ADAM-15
in vascular diseases, and
ADAM-15
was found to be associated with
atherosclerosis
. Other studies also pointed at
ADAM-15
as a mediator of rheumatoid arthritis and intestinal inflammation as well as inherent angiogenesis. The roles of
ADAM-15
in these diseases appear to involve mechanisms as different as cell-cell interactions, cell-extracellular matrix (ECM) interactions, and shedding activity. Here we review and discuss these recent discoveries pointing to
ADAM-15
as a mediator of mechanisms underlying inflammation and as a possible therapeutic target for prevention of inflammatory diseases.
...
PMID:ADAM-15: a metalloprotease that mediates inflammation. 1790 25
