The growth of atherosclerotic plaques in blood vessels is harmful, not least because it restricts blood flow, even blocking entire vessels in the worst cases. The vast majority of cardiovascular mortality results from the rupture of fatty, unstable plaques, however, leading to stroke and heart attack when the fragments block downstream vessels. If the development of plaque instability could be slowed or reversed, this would have a sizable impact on cardiovascular mortality - even given that this goal is a step down from reversal of plaque in general. Thus researchers are interested in finding the mechanisms that determine whether a plaque is more fatty and less fibrous, and thus more prone to rupture.
Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications - myocardial infarction and stroke - are the leading cause of mortality worldwide. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis. However, the role of TREM2 in atherosclerosis is not fully known.
Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.
Link: https://doi.org/10.1...161-024-00429-9
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