JAM-A Junctional Adhesion Molecule A or Janus Acting Mediator in Atheroscierosis

Martin Schmitt



Atherosclerosis is a chronic inflammation of the arterial wall and causes inter
alia rearrangement of cellular and subcellular components. Besides some other
diseases like thromboembolic disease, rhythm disorders and hypertension,
atherosclerosis is the main contributor to cardiovascular diseases.
Atherosclerotic lesions are mediated by modified low density lipoproteins (LDL)
triggered immune cell influx, accumulation of dead mononuclear and vascular
cells, reorganization of smooth muscle cells (SMC) as well as deposition of
extracellular matrix like collagen. Most atherosclerotic lesions cause luminal
narrowing comprising altered shear stress conditions, until unstable lesion
rupture releases prothrombotic material into the lumen, initiating coagulation
and causing occlusion. Dependent on the site of occlusion this may lead to
myocardial infarction or stroke, two of the most important sources for illness and
death in developed countries1-3.

The onset of atherosclerosis is represented by the formation of a “fatty
streak”, an accumulation of highly lipid-laden macrophages4. In a classification
of plaque stages by Virmani and colleagues those intimal xanthomas still count
for the non-atherosclerotic intimal lesions without necrotic core or fibrous
depositions covering the lipid core, often referred to as fibrous cap5. Intimal
macrophages phagocytose excess lipids, transform into “foam cells” and
contribute together with activated endothelial cells and further intimal immune
cells to the inflammatory milieu by secreting a great variety of cytokines, like
Interleukin (IL)-1 and -6, and tumor necrosis factor (TNF)-α6, chemokines and
proteases. Progressive atherosclerotic lesions finally evolve from this enhanced
secretion of atherogenic factors. Those lesion stages were categorized by
Virmani et al. as pathological intimal thickening comprising SMCs in a
proteoglycan-rich matrix and extracellular lipid accumulations and as fibrous
cap atheroma containing a well-formed necrotic core and a covering fibrous
cap. Finally, matrix-metallo protease mediated weakening of the fibrous cap
results in a higher susceptibility to plaque rupture followed by vessel occlusion.



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