The molecular basis of vulnerable plaque: potential therapeutic role for immunomodulation.
OBJECTIVE
Atherosclerosis is a chronic inflammatory/immune disease involving multiple cell types including monocytes-macrophages, T-lymphocytes, mast cells, and endothelial cells. Through recent studies the role of the immune system on development of atherosclerosis and approaches to modulate this response are being elucidated.


RESULTS
The use of statins, PPARgamma agonists or lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors may play a role in reducing progression of atherosclerosis through immunomodulatory pathways. Oxidized LDL biases development toward the pro-inflammatory T-cell Th1 subset and recruits macrophages into the vascular wall. IFNgamma, produced by Th1 cells, inhibits PPARgamma effects. Lp-PLA2 levels correlate with an increased risk of recurrent ischemic events in patients presenting with acute coronary syndromes or myocardial infarction.


CONCLUSIONS
Recent research has shown that immune pathways play a major role in the development and progression of atherosclerosis. Commonly used medications, specifically statins and some PPARgamma agonists, have demonstrated anti-inflammatory/immune effects unrelated to their primary mode of action. Treatment of infectious agents has proven elusive in the clinical arena. Novel agents targeting immune and inflammatory pathways may prove beneficial in reducing progression and instability of the atherosclerotic plaque.
Wilensky
Robert L
RL
University of Pennsylvania, Philadelphia, Pennsylvania, USA. Robert.wilensky@uphs.upenn.edu
Hamamdzic
Damir
D
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007155:Immunologic Factors; D047495:PPAR gamma; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase