Lipid Immunology

The Intracellular Cholesterol Landscape: Dynamic Integrator of the Immune Response

Cholesterol has typically been considered an exogenous, disease-related factor in immunity; however, recent literature suggests that a paradigm shift is in order. Sterols are now recognized to ligate several immune receptors. Altered flux through the mevalonic acid synthesis pathway also appears to…
Lately, there has been much fuss about false news pervading social media. One erroneous medical news recurrently making the rounds on the Internet is the one about bad cholesterol LDL actually making one live longer, and that statins are toxins proffered by unconscionable doctors in cahoots with big pharmas for blood money. The unfortunate consequence may be that some patients at high risk for cardiovascular disease may stop their medication to their peril.
Study design and statistical methodology lie at the heart of this “controversy”. What doesn’t help better understanding is that the relationship between lipids and cardiovascular events (heart attack, stroke) is not a straightforward one. The lynchpin is INFLAMMATION.

Lipids affect immune cells. Omega-3 fatty acids, for example, are anti-inflammatory. LDL, when oxidised, drives inflammation. Macrophages invade artery walls, bloat up with oxLDL into foam cells, and form the atheromatous plaque; which narrows the artery gradually, or ruptures suddenly (eg shearing force from high blood pressure) to obstruct blood flow.
Statins reduce cardiovascular risks not so much by merely lowering LDL, but by inhibiting macrophage proliferation and inflammatory activity.
This explains why not everyone with high LDL gets a heart attack: oxidisation of LDL (predisposed by smoking and diabetes) is the real culprit. It also explains why Ezetimibe, which lowers LDL powerfully, does not reduce heart attack risk. And it explains why patients with chronic inflammatory diseases like Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis have higher cardiovascular risks.
It’s all about INFLAMMATION.

Free Fatty Acids: A Role in RA?

Elevated in both preclinical and established disease

Statins & the Risk of RA

Image result for ldl inflammation

Statins have anti-inflammatory/immunomodulatory effects that may be useful in preventing rheumatoid arthritis (RA), but previous observational studies…

Statins reduce atherosclerosis by inhibiting the enzyme HMG-CoA-reductase, thereby lowering LDL production.  They also inhibit  the proliferation of monocytes and macrophages, which would otherwise move into the blood vessel wall, “mop up” the oxidized LDL, morph into foam cells, and eventually form the atheromatous plaque.

Don’t do half-hearted measures.  The higher the dose, the longer you live!