Proresolving receptor tames inflammation in atherosclerosis

Mena, Hebe Agustina; Spite, Matthew

doi:10.1172/jci155240

Cited by 5 publications

(7 citation statements)

References 25 publications

(34 reference statements)

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“… 20 , 22 Macrophages within or near atherosclerotic plaques continue to become defective in efferocytosis, as the expression of GPR32 receptors for SPM is reduced with constant inflammatory stimuli, further delaying the regional resolution of inflammation. 12 , 23 Taken together, unresolved arterial inflammation continuously recruits inflammatory cells to expanding plaques, which serve as long-lasting stimulators for the synthesis of RvD1, therefore leading to regional and circulatory elevation of RvD1 levels. As a consequence of ongoing inflammation, plaque rupture could therefore be associated with a high circulating level of RvD1 ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

“… 11 In contrast, the expression of G protein-coupled receptor 32 (GPR32), which is one of the receptors for RvD1, is substantially reduced in human atherosclerotic lesions. 12 Although the underlying mechanisms have not been fully determined, successful resolution of vascular inflammation seems to be promoted by RvD1, which rescues macrophages from apoptosis induced by oxidative stress and restores regional efferocytosis of apoptotic cells. 13 These findings suggest that RvD1 is involved in the development of atherosclerosis as a pro-resolving antioxidant.…”

Section: Introductionmentioning

confidence: 99%

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Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction

Chen,

Li,

Sheng

et al. 2023

JIR

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Background As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI). Methods A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features. Results The median RvD1 level was 129.7 (56.6–297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20–3.66, P = 0.010), healed plaques (≥246.4 pg/mL, OR: 2.17, 95% CI: 1.11–4.24, P = 0.023), and calcification (≥293.38 pg/mL, OR: 2.10, 95% CI: 1.21–3.66, P = 0.008) at culprit lesions. Conclusion Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction

Chen,

Li,

Sheng

et al. 2023

JIR

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“…Recently, GPR32, a receptor for pro-resolving lipid mediators like resolvin D1, was reported to be reduced in human atherosclerotic lesions. Exhilaratingly, the lesion area and necrosis of atherosclerotic plaques were observably decreased when this receptor was overexpressed in mice ( 111 ). However, because the applied detection methods for necrosis have not been found, it has not been investigated extensively as apoptosis.…”

Section: Macrophage Necrosis In Atherosclerotic Plaque Formationmentioning

confidence: 99%

Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation

Cao

Wang

et al. 2022

Front. Immunol.

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Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS.

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“…Modulation of human macrophage responses has also been reported, with GPR32 promoting a pro‐resolving phenotype (Schmid et al, 2016). Further, a recent elegant study revealed an atheroprotective role of GPR32 in a transgenic mouse colony lacking endogenous FPR2, a feature associated with modulation of leukocyte recruitment and macrophage efferocytosis (Arnardottir et al, 2021; Mena & Spite, 2021).…”

Section: Fpr2 and Other Pro‐resolving Receptorsmentioning

confidence: 99%

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

Qin

Norling

Vecchio

et al. 2022

British J Pharmacology

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We discuss the fascinating pharmacology of formylpeptide receptor 2 (FPR2; often referred to as FPR2/ALX since it binds lipoxin A4). Initially identified as a low‐affinity ‘relative’ of FPR1, FPR2 presents complex and diverse biology. For instance, it is activated by several classes of agonists (from peptides to proteins and lipid mediators) and displays diverse expression patterns on myeloid cells as well as epithelial cells and endothelial cells, to name a few. Over the last decade, the pharmacology of FPR2 has progressed from being considered a weak chemotactic receptor to a master‐regulator of the resolution of inflammation, the second phase of the acute inflammatory response. We propose that exploitation of the biology of FPR2 offers innovative ways to rectify chronic inflammatory states and represents a viable avenue to develop novel therapies. Recent elucidation of FPR2 structure will facilitate development of the anti‐inflammatory and pro‐resolving drugs of next decade.

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Proresolving receptor tames inflammation in atherosclerosis

Cited by 5 publications

References 25 publications

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction

Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation

Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35

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