There is a growing body of evidence that
dihydropyridine-based
calcium antagonists (DHPs) improve endothelial function, thus slowing the development and progression of
atherosclerosis. We have previously shown that
nifedipine, one of the most popular DHPs, inhibits
tumor necrosis factor-alpha (
TNF-alpha)-induced
reactive oxygen species generation and subsequent
monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVEC). However, the molecular mechanism underlying this phenomenon remains to be elucidated. CD40, a
cell surface receptor that belongs to
TNF-alpha receptor, has been associated with the pathogenesis of chronic inflammatory diseases such as
atherosclerosis. In this study, we investigated the involvement of CD40 in MCP-1 suppression by
nifedipine in
TNF-alpha-exposed HUVEC.
Nifedipine completely inhibited
TNF-alpha-induced upregulation of CD40
mRNA levels in HUVEC. Furthermore, antibody against human CD40 was found to significantly inhibit upregulation of MCP-1
mRNA levels in
TNF-alpha-exposed HUVEC. These results demonstrate that
nifedipine could inhibit the
TNF-alpha-induced upregulation of MCP-1
mRNA levels via suppression of CD40 expression in HUVEC. Our present study suggests that blockade of CD40 signaling in endothelial cells may be a molecular target for the vasculoprotective property of
nifedipine.