Omega-3 Fatty Acids Against Vascular Calcification

A new strategy to combat atherosclerosis: researchers at LMU try to activate the body’s own healing processes.

vascular calcification
The diagram shows how resolution-inducing lipid mediators “switch on” healing macrophages. Macrophages are depicted (CD68 red, CD206 green) in the atherosclerotic lesion after administration of Resolvin D2 and Maresin 1. (Illustration: O. Söhnlein, LMU)

Atherosclerosis – commonly known as “hardening of the arteries” – occurs when deposits on the inner walls of vessels lead to chronic inflammation and narrowing of the vessels. That can restrict blood flow or block it entirely, ultimately triggering a cardiac infarction or a stroke. Treatment strategies up to now focus primarily on inhibiting the inflammation reaction. Researchers led by Professor Oliver Söhnlein from the Institute for Cardiovascular Prevention at LMU have now developed a completely new treatment strategy which focuses on stimulating the body’s own healing processes. Active substances contained in fish oil and other sources play a key role in this, improving atherosclerosis in mice tested. The scientists reported their results in the professional journal Circulation Research.

In recent years, research results have shown that not only the occurrence, but also the resolution of inflammations is an active process of the immune defense system. “With atherosclerosis, this ‘inflammation resolution program’ is disrupted, so the inflammation becomes chronic,” explained Söhnlein. Special signal molecules made of essential fatty acids – known as lipid mediators – are decisive for the progress of inflammation and its resolution. These inflammation-promoting lipid mediators are active at first in acute inflammations. Inflammation-inhibiting lipid mediators assume the role of regulation to stop the reaction. For this process to work, both types of lipid mediators must be present in a balanced relationship.

“We were able to demonstrate that this balance is disturbed in cases of atherosclerosis”, Söhnlein commented. Normally, inflammatory responses should be stopped after the acute phase has run its course, characterized by an increase in the concentration of inflammation-inhibiting lipid mediators. Instead, the opposite occurs. As the scientists showed, in atherosclerotic tissue, lipid mediators were in fact reduced, and the inflammation continued. “By administering the inflammation-inhibiting lipid mediators Maresin 1 and Resolvin D2, we were able to correct this imbalance and relieve atherosclerosis in mice,” Söhnlein explained. Maresin 1 and Resolvin D2 are formed from omega-3 fatty acids, which are present in fish oil among other things. Fish oil has long been said to have a positive influence on health.

From a functional perspective, the scientists used the lipid mediators to influence macrophages, the scavenger cells of the immune system. Macrophages accumulate in atherosclerotic plaques and can contribute to the progress of inflammation by consuming blood lipids in excess leading to self-destruction. But they also have an important role in healing inflamed tissue, because they remove dead cells and stimulate the production of smooth muscle cells. Söhnlein noted that “Administering lipid mediators promotes this effect of relieving inflammation, i.e. steers the activity of the macrophages in a desired direction. It would be desirable in future studies to investigate whether the results of testing in mice also apply to humans.” (Circulation Research 2016)