Chronic endothelial injury and dysfunction resulting from the presence of atherosclerosis, and the inflammatory and metaplastic changes that it induces in the vascular subendothelial space
, are central to our present understanding of vascular and atherosclerotic pathogenesis.
The vasculitis involves destruction of small to medium-sized arteries that contain an inflammatory infiltrate within the vessel wall and subendothelial space
, leading to destruction of the elastic lamina (figure 1).
Oxidized low-density lipoprotein (LDL) within the subendothelial space
is converted by Lp-PLA2 into oxidized free fatty acids and lysophoshatidylcholine (Macphee et al.
LDL particle circulates in plasma, including a fraction, which reenters the circulation from the subendothelial space
When low-density lipoprotein (LDL) cholesterol infiltrates the subendothelial space
and becomes oxidised, a complex inflammatory process is triggered.
It is known that LDL could pass, via transcytosis, through the vascular endothelium to reach the subendothelial space
The subendothelial space
contained inflammatory infiltrates, predominantly neutrophils that were often multilayered and present in loose aggregates.
Binding of circulating monocytes to vascular endothelial cells and their subsequent transendothelial migration into the subendothelial space
are mediated by inducible cell adhesion molecules (CAMs) expressed on the surface of endothelial cells.
Once oxidized, LDL is taken up by macrophages (cells of the immune system) that occupy the subendothelial space
of the blood vessel wall and eventually form foam cells and fatty streaks (early atherosclerosis), ultimately forming artery-narrowing plaques and setting the stage for heart attacks.
CRP stimulates the production of cytokines and interleukins by macrophages, decreases nitric oxide production, stimulates endothelial adhesion molecule expression, and can fix complement in the subendothelial space
The initial stage of atherosclerosis is the formation of a fatty streak in arterial vessels, which involves the deposition of lipid, in particular cholesterol, in the subendothelial space
of arterial intima (1).
Electron microscopy findings include subendothelial space
widening of the endothelial cells and separation from the underlying GBM in acute injury, with duplication of the GBMs as a sign of chronicity.