Hi, I'm trying to evaluate a paper that looks into IL-1, MMP3 and atherosclerotic plaque stability and would really appreciate advice if anyone has read this paper or knows about the subject ; "Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice"- Journal of Clinical Investigation.
1. Are the brachiocephalic artery and aortic root the most representative vessels to look at when studying the role of proinflammatory cytokines on plaque stability?
2. Does it provide enough evidence to suggest clinical therapies that promote IL-1 should be used and how representative is the mouse model?
Also, other opinions on this paper are also greatly welcomed.
Thank you.
1. Atherosclerosis has a systemic manifestation. However, atherosclerotic lesions develop preferentially and/or earlyer at sites where blood flows is non-laminar, such as around vascular bifurcations.
2. The major interest of the article you refer to is that they found opposite results as compared to what the authors were expecting.
In fact, there are multiple studies that point in the opposite direction, that is: IL-1 and IL-2 show pro-atherosclerotic effects. Very recently, the large RCT CANTOS showed that inhibition of IL-1 beta prevents cardiovascular events in patients with previous Myocardial Infarction.
These intriguing results just raise the point that things are a bit more complex than previous hypotheses.
On this basis I don't believe it justify the development of a therapeutic approach.
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