The energy metabolism of immune cells influences the progression of arteriosclerosis

The energy metabolism of immune cells influences the progression of arteriosclerosis

Two complementary studies show how inadequate energy supply in macrophages, important immune cells in artery walls, drives the progression of atherosclerosis - and how this knowledge could lead to better diagnostics and future therapies. The University of Eastern Finland was centrally involved in both studies.

Atherosclerosis – the buildup of fatty deposits in the arteries – is the leading cause of heart attacks and strokes worldwide. Although there has long been a focus on the role of cholesterol in plaque formation, scientists are increasingly recognizing that the immune system plays a critical role in whether plaques remain stable or become unstable and therefore susceptible to rupture, which can lead to heart attacks or strokes.

In the two newly published studies, an international team of researchers showed that poor availability of the amino acid glutamine in macrophages may be responsible for the worsening of arterial plaques. The researchers also identified new ways to detect dangerous plaques.

Immune cells need fuel to repair damaged arteries

Macrophages are the body's cleansing powers. In arterial plaques, they absorb fats, remove dying cells and help repair damaged tissue. But to fulfill these protective tasks, macrophages need energy.

In the first study, published inNatural metabolismthe researchers found that macrophages rely heavily on glutamine uptake from their environment to fuel their restorative functions. A specific transport protein, SLC7A7, acts as a gate that allows glutamine to enter the cell. When this gate is blocked, macrophages lose energy and deteriorate their performance, resulting in larger and more unstable plaques, which is a known risk factor for heart attacks and strokes in humans.

Reduced activity of this pathway has also been linked to more dangerous plaque characteristics in human artery samples.

These results suggest that restoring or supporting macrophage metabolism could one day help stabilize plaques and prevent heart attacks or strokes.”

Professor Minna Kaikkonen-Määttä, University of Eastern Finland

New tools to identify high-risk plaques

The second study, published inCardiovascular researchbuilds on this biological insight and moves towards the clinic. By studying macrophages using advanced single-cell technologies, researchers identified protein markers such as TREM2, FOLR2 and SLC7A7 that highlight high-risk plaques.

Based on these markers, PET imaging could be used to detect the activity of inflammatory plaques and not just the size of the plaques.

The researchers also found that soluble TREM2 in the blood can help distinguish between stable and symptomatic plaques, raising the possibility of a future blood test to identify patients at highest risk.

The research reflects close international collaboration, with the University of Barcelona, ​​among others, contributing to both studies. The first study was led by the Université Côte d’Azur, while the second was co-led by the University of Turku.

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