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Effect Of Eicosapentaenoic Acid (EPA) On The Pathogenesis Of Atherosclerosis

|Includes: Amarin Corporation PLC (AMRN)

Vascepa has been approved to reduce trigs in patients who have over 500mg/dL total trigs in their blood. People often ask, is it really important to lower trigs? Will lowering trigs ultimately be beneficial in reducing major cardiovascular events?

These are fair questions, however, I feel that people who limit themselves to just the question of very high trigs are missing the point. Vascepa (EPA), does much more than just lower a patient's trig level. It lowers a variety of other cardio-risk markers, e.g. lp-PLA2, hs CRP, VLDL to name a few...

Not only does it lower these markers, it is also readily incorporated into atherosclerotic plaques themselves, making them more stable and less inflamed.

Here is a study, Orally administered Eicosapentaenoic Acid reduces and stabilizes atherosclerotic lesions in Apo-E deficient mice, that was run by Department of Advanced Clinical Science and Therapeutics, University of Tokyo Graduate School of Medicine, and Mochida Pharma.

Look at this figure showing the extent of fatty plaque build-up in control mice vs. EPA supplemented mice revealed using Sudan IV staining:

 western-type diet (0.15% cholesterol, 15% butter) without supplemented with 5% EPA (8 g/kg/day; EPA group, n = 7) or not (control group, n = 5) for 13 weeks using Sudan IV staining

Mice were fed a western-type diet (0.15% cholesterol, 15% butter) supplemented with 5% EPA (8 g/kg/day; EPA group, n = 7) or not (control group, n = 5) for 13 weeks

Clearly, EPA supplemented mice fared much better in terms of maintaining a relatively healthy vasculature despite eating a "western-type' diet. These results fall in line with many other studies that have shown EPA's ability to reduce inflammation and to stabilize, or reverse plaque build up. Here are their key findings in conclusion:

"En face Sudan IV staining of the aorta and oil red O-staining of the aortic sinus revealed that EPA significantly suppressed the development of atherosclerotic lesions. We also observed anti-atherosclerotic effects of EPA in LDL-receptor-deficient mice. The lesions of the EPA group contained more collagen (19.6 ± 2.4% vs. 32.9 ± 3.9%, p < 0.05) and smooth muscle cells (1.3 ± 0.2% vs. 3.6 ± 0.8%, p < 0.05) and less macrophages (32.7 ± 4.1% vs. 14.7 ± 2.0%, p < 0.05). Pretreatment with EPA attenuated the up-regulation of VCAM-1, ICAM-1 and MCP-1 in HUVECs as well as the expression of MMP-2 and MMP-9 in macrophage-like cells induced by TNF-α. The anti-inflammatory effects of EPA were abrogated when the expression of peroxisome proliferator-activated receptor alpha (PPARα) was suppressed. EPA may potentially reduce and stabilize atherosclerotic lesions through its anti-inflammatory effects."

So, as you can see, lowering trigs is just one of the many beneficial results of increasing one's intake of EPA... Currently, Amarin is running a trial (REDUCE-IT) that is set up to show Cardiovascular Outcome improvement of Vascepa + Statin over a regimen of just a Statin alone.

Whereas statins reduce the culprits of plaque build up which improve plaque stability over time, EPA gets right to the core of the problem, infiltrating plaques themselves to clean up the inflammation "signalers", almost akin to riot police clearing out a mob and quieting them down.

If REDUCE-IT matches or bests the results from JELIS, Vascepa should be a common place name, similar to Lipitor or Crestor.

Disclosure: I am long AMRN.