Different monocyte phenotypes result in proresolving macrophages in conjugated linoleic acid‐induced attenuated progression and regression of atherosclerosis

Bruen, Robyn; Curley, Sean; Kajani, Sarina; Lynch, Gina; O’Reilly, M.; Dillon, Eugene; Fitzsimons, Stephen; Mthunzi, Liberty; McGillicuddy, Fiona C.; Belton, Orina

doi:10.1096/fj.201900922r

Cited by 8 publications

(8 citation statements)

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“…CLA, a pro-resolving lipid mediator, has previously been shown to attenuate progression and induce regression of atherosclerosis via regulation of monocyte function and phenotype (3)(4)(5). However, the molecular mechanisms underlying the atheroprotective effect of CLA have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…ApoE −/− mice fed a 1% cholesterol chow diet (1% CD) or normal chow diet (ND) group were used as controls. ApoE −/− mice were randomized at 40 days to receive either a ND for 12 weeks, a 1% CD for 12 weeks or a 1% CD for 12 weeks where the final 4 weeks were supplemented with 1% CLA blend (1% CD + CLA) to induce regression (3)(4)(5).…”

Section: Animals and Dietsmentioning

confidence: 99%

“…The two most abundant isomers are cis-9, trans-11(c-9,t-11) and trans-10, cis-12 (t-10,c-12). We have previously shown that dietary administration of an isomeric blend of these isomers; c-9,t-11: t-10,c-12, in an 80:20 ratio, halts progression and induces regression of pre-established atherosclerosis in vivo via alteration of monocyte/macrophage function (3,4). Furthermore, the atheroprotective effects of CLA blend were mediated by increased interleukin (IL)-10 and phosphorylated-signal transducer and activator of transcription 3 (p-STAT-3) signaling and the priming of both bone marrowderived macrophages (BMDMs) and human peripheral blood monocytes toward an M2-like phenotype (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…ApoE −/− mice fed a 1% CD for 8 weeks, and maintained on this diet for a further 8 weeks with 1% CLA supplementation showed reduced aorta lesion size by approximately 30% when compared to controls (3). The model has been extensively validated, most recently by Bruen et al(4). In a separate 12-week study using this model, we previously performed transcriptomic analysis on aortae from ApoE −/− mice fed either a 1% CD or a 1% CD supplemented with 1% CLA blend for the final 4 weeks.…”

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microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

et al. 2020

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BackgroundAtherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis in vivo. In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD).MethodsmiR-155 expression was quantified in aortae from ApoE−/− mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, cis-9,trans-11:trans-10,cis-12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on ex vivo human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD.ResultsHere, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression in vivo. CLA blend also decreased miR-155 expression in vitro in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs.ConclusionmiR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis in vivo and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Animals and Dietsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

et al. 2020

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“…In a recent experimental study, Bruen et al showed that conjugated linoleic acid (CLA), which is an antiinflammatory lipid, can induce regression of atherosclerosis in ApoE -/mice. In mice fed CLA, more monocytes differentiated into anti-inflammatory M2 macrophages [30]. Sun et al fed ApoE -/model mice phenytoin, a non-selective voltage-gated sodium channels antagonist, and the mice subsequently exhibited increased levels of anti-inflammatory monocytes and decreased levels of proinflammatory monocytes [31].…”

Section: Database Analysismentioning

confidence: 99%

Crucial Gene Identification in Carotid Atherosclerosis Based on Peripheral Blood Mononuclear Cell (PBMC) Data by Weighted (Gene) Correlation Network Analysis (WGCNA)

et al. 2020

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Background: Many patients are not responsive or tolerant to medical therapies for carotid atherosclerosis. Thus, elucidating the molecular mechanism for the pathogenesis and progression of carotid atherosclerosis and identifying new potential molecular targets for medical therapies that can slow progression of carotid atherosclerosis and prevent ischemic events are quite important. Material/Methods: We downloaded the expression profiling data of PBMC in Biobank of Karolinska Endarterectomy (BiKE, GSE21545) for GEO. The WGCNA and DEG screening were conducted. The co-expression pattern between patients with ischemic events (the events group) and patients without ischemic events (the no-events group) were compared. Then, we identified hub genes of each module. Finally, the DEG co-expression network was constructed and MCODE was used to identify crucial genes based on this co-expression network. Results: In the study, 183 DEGs were screened and 8 and 6 modules were assessed in the events group and no-events group, respectively. Compared to the no-events group, genes associated with inflammation and immune response were clustered in the green-yellow module of the events group. The hub gene of the green-yellow module of the events group was KIR2DL5A. We obtained 1 DEG co-expression network, which has 16 nodes and 24 edges, and we detected 5 crucial genes: SIRT1, THRAP3, RBM43, PEX1, and KLHDC2. The upregulated genes (THRAP3 and RBM43) showed potential diagnostic and prognostic value for the occurrence of ischemic events. Conclusions: We detected 8 modules for the events group and 6 modules for the no-events group. The hub genes for modules and crucial genes of the DEG co-expression network were also identified. These genes might serve as potential targets for medical therapies and biomarkers for diagnosis and prognosis. Further experimental and biological studies are needed to elucidate the role of these crucial genes in the progression of carotid atherosclerosis.

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10,12-Conjugated linoleic acid supplementation improves HDL composition and function in mice

Vaisar¹,

Wang²,

Omer³

et al. 2022

Journal of Lipid Research

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Different monocyte phenotypes result in proresolving macrophages in conjugated linoleic acid‐induced attenuated progression and regression of atherosclerosis

Cited by 8 publications

References 50 publications

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

microRNA-155 Is Decreased During Atherosclerosis Regression and Is Increased in Urinary Extracellular Vesicles During Atherosclerosis Progression

Crucial Gene Identification in Carotid Atherosclerosis Based on Peripheral Blood Mononuclear Cell (PBMC) Data by Weighted (Gene) Correlation Network Analysis (WGCNA)

10,12-Conjugated linoleic acid supplementation improves HDL composition and function in mice

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