|
|
|
front |1 |2 |3 |4 |5 |6 |7 |8 |9 |10 |11 |12 |13 |14 |15 |16 |17 |18 |19 |20 |21 |22 |23 |24 |review |
 |
Oxidation of
low-density lipoprotein (LDL) initiates the atherosclerotic process in the
vessel wall by acting as a potent stimulus for the induction of inflammatory
gene products in vascular endothelial cells. By activating the NFk B
transcription factor, oxidized LDL (oxLDL) stimulates increased expression
of cellular adhesion molecules. There are several different types of
adhesion molecules with specific functions in the endothelial leukocyte
interaction: The selectins tether and trap monocytes and other leukocytes.
Importantly, vascular cell adhesion molecules (VCAMs) and intercellular
adhesion molecules (ICAMs) mediate firm attachment of these leukocytes to
the endothelial layer.
OxLDL also augments expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage colony stimulating factor (M-CSF). MCP-1 mediates the attraction of monocytes and leukocytes and their diapedesis through the endothelium into the intima. M-CSF plays an important role in the transformation of monocytes to macrophage foam cells. Macrophages express scavenger receptors and take up and internalize oxLDL in their transformation into foam cells. Migration of smooth muscle cells (SMCs) from the intima into the media is another early event initiating a sequence that leads to formation of a fibrous atheroma. Kinlay et al. J Cardiovasc Pharmacol. 1998;32(suppl 3)S62-S66.
|