Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
By M. Bäck, Arif Yurdagul, I. Tabas, K. Öörni, P. Kovanen. Nature Reviews Cardiology, 2019
1,213 citations recorded by the source corpus.
Atherosclerosis is a lipid-driven inflammatory disease of the arterial intima in which the balance of pro-inflammatory and inflammation-resolving mechanisms dictates the final clinical outcome. Intimal infiltration and modification of plasma-derived lipoproteins and their uptake mainly by macrophages, with ensuing formation of lipid-filled foam cells, initiate atherosclerotic lesion formation, and deficient efferocytotic removal of apoptotic cells and foam cells sustains lesion progression. Defective efferocytosis, as a sign of inadequate inflammation resolution, leads to accumulation of secondarily necrotic macrophages and foam cells and the formation of an advanced lesion with a necrotic lipid core, indicative of plaque vulnerability. Resolution of inflammation is mediated by specialized pro-resolving lipid mediators derived from omega-3 fatty acids or arachidonic acid and by relevant proteins and signalling gaseous molecules. One of the major effects of inflammation resolution mediators is phenotypic conversion of pro-inflammatory macrophages into macrophages that suppress inflammation and promote healing. In advanced atherosclerotic lesions, the ratio between specialized pro-resolving mediators and pro-inflammatory lipids (in particular leukotrienes) is strikingly low, providing a molecular explanation for the defective inflammation resolution features of these lesions. In this Review, we discuss the mechanisms of the formation of clinically dangerous atherosclerotic lesions and the potential of pro-resolving mediator therapy to inhibit this process.Atherosclerosis is characterized by low-grade, chronic inflammation, and the balance between pro-inflammatory and inflammation-resolving mechanisms dictates the clinical outcomes. This Review discusses the specific causes of inflammation and the mechanisms underlying the impaired resolution of inflammation that characterize clinically dangerous atherosclerotic lesions and highlights the potential of pro-resolving mediator therapy for the prevention and treatment of atherosclerotic cardiovascular disease.Key pointsModified lipoproteins and cholesterol crystals accumulate in the arterial intima and induce foam cell formation and inflammation.Defective efferocytosis of apoptotic foam cells leads to necrotic core formation.Defective efferocytosis is a sign of failure in the resolution of inflammation.Inflammation resolution is mediated by specialized pro-resolving lipid mediators, proteins and signalling gases.Improvement of the balance between pro-inflammatory and pro-resolving processes enables the resolution of inflammation.Pro-resolving mediator therapy could be a novel approach to suppressing the formation of clinically dangerous atherosclerotic lesions.
Subfields: Epidemiology, Immunology, Nutrition and Dietetics
View Paper: https://www.semanticscholar.org/paper/5edaa46048641b51984fe4354e9f471870f21c81
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Citations in the corpus
- Atherosclerosis: Recent developments (2022, background): “It involves a functional switch from proinflammatory to antiinflammatory macrophages and is mediated by certain lipids (known as resolvins and lipoxins), proteins, and nitric oxide (Bäck et al., 2019).”
- Inflammation and atherosclerosis: signaling pathways and therapeutic intervention (2022, background): “1c).(93) CD4 and CD8 T cells in the plaques from symptomatic patients with recent cardiovascular events were activated, differentiated, and exhausted compared with their blood counterparts.”
- Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “They are attracted to the arteries by chemokines, such as CCL2 secreted by activated endothelial cells (71–77) and take up lipids within the subendothelial space to differentiate into foam cells (76, 78).”