The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Åkra, Sissel; Seljeflot, Ingebjørg; Braathen, Bjørn; Bratseth, Vibeke; Hansen, Charlotte Holst; Arnesen, Harald; Tønnessen, Theis; Solheim, Svein

doi:10.1016/j.athplu.2022.03.005

Cited by 3 publications

(8 citation statements)

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“…CD163 and CD68, CD3, and CD31, the most representative markers of macrophages, T cells and endothelial cells, respectively, were analyzed in SAT, PAT, and EAT of CHD patients to detect the specific cellular subtypes in each AT compartment. The previously analyzed markers were detectable in the three AT compartments, with an overall similar distribution (27). When matching these data with L-Gal 9, CD206, and NOS2, we found that L-Gal 9 expression in PAT and EAT positively correlated to CD3 expression (r = 0.37, p = 0.008 and r = 0.373, p = 0.007, respectively; although no longer statistically significant after Bonferroni's correction; Figure 3).…”

Section: Correlations Between L-gal 9 Cd206 and Nos2 Expression And C...mentioning

confidence: 59%

“…Before anesthesia, arterial blood samples were collected. More details have previously been published (27).…”

Section: Patientsmentioning

confidence: 99%

“…The ΔΔCt method was applied to determine the mRNA levels in each reaction, using the β2-Microglobulin (Hs99999907_m1) as the normalizer internal gene, and expressed as relative quantification (RQ) to a reference sample (28). Gene expression of CD163, CD68, CD3, and CD31, representing macrophages, T cells and endothelial cells, respectively, was analyzed through RT-PCR to determine the different cell types present in each AT sample, as previously described (27).…”

Section: Laboratory Analysesmentioning

confidence: 99%

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Macrophage polarization markers in subcutaneous, pericardial, and epicardial adipose tissue are altered in patients with coronary heart disease

Papotti

Opstad²,

Åkra³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundEpicardial and pericardial adipose tissue (EAT and PAT) surround and protect the heart, with EAT directly sharing the microcirculation with the myocardium, possibly presenting a distinct macrophage phenotype that might affect the inflammatory environment in coronary heart disease (CHD). This study aims to investigate the expression of genes in different AT compartments driving the polarization of AT macrophages toward an anti-inflammatory (L-Galectin 9; CD206) or pro-inflammatory (NOS2) phenotype.MethodsEAT, PAT, and subcutaneous (SAT) biopsies were collected from 52 CHD patients undergoing coronary artery bypass grafting, and from 22 CTRLs undergoing aortic valve replacement. L-Galectin9 (L-Gal9), CD206, and NOS2 AT gene expression and circulating levels were analyzed through RT-PCR and ELISA, respectively.ResultsL-Gal9, CD206, and NOS2 gene expression was similar in all AT compartments in CHD and CTRLs, as were also L-Gal9 and CD206 circulating levels, while NOS2 serum levels were higher in CHD (p = 0.012 vs. CTRLs). In CTRLs, NOS2 expression was lower in EAT vs. SAT (p = 0.007), while in CHD patients CD206 expression was lower in both SAT and EAT as compared to PAT (p = 0.003, p = 0.006, respectively), suggestive of a possible macrophage reprogramming toward a pro-inflammatory phenotype in EAT. In CHD patients, NOS2 expression in SAT correlated to that in PAT and EAT (p = 0.007, both), CD206 expression correlated positively to L-Gal9 (p < 0.001) only in EAT, and CD206 expression associated with that of macrophage identifying markers in all AT compartments (p < 0.001, all). In CHD patients, subjects with LDL-C above 1.8 mmol/L showed significantly higher NOS2 expression in PAT and EAT as compared to subjects with LDL-C levels below (p < 0.05), possibly reflecting increased cardiac AT pro-inflammatory activation. In SAT and PAT, CD206 expression associated with BMI in both CHD and CTRLs (p < 0.05, all), and with L-Gal9 in EAT, however only in CTRLs (p = 0.002).ConclusionCHD seems to be accompanied by an altered cardiac, and especially epicardial AT macrophage polarization. This may represent an important pathophysiological mechanism and a promising field of therapy targeting the excessive AT inflammation, in need of further investigation.

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Section: Correlations Between L-gal 9 Cd206 and Nos2 Expression And C...mentioning

confidence: 59%

“…Before anesthesia, arterial blood samples were collected. More details have previously been published (27).…”

Section: Patientsmentioning

confidence: 99%

Section: Laboratory Analysesmentioning

confidence: 99%

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Macrophage polarization markers in subcutaneous, pericardial, and epicardial adipose tissue are altered in patients with coronary heart disease

Papotti

Opstad²,

Åkra³

et al. 2023

Front. Cardiovasc. Med.

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“…The β2-microglobulin (Hs99999907_m1, Applied Biosystems) was used as the normalizer internal gene, and relative quantification of SIRT1 mRNA and NAMPT mRNA levels were determined applying the ΔΔCt method [ 26 ]. Gene expression of the NLRP3-related inflammatory markers (NLRP3, Caspase-1, IL-18, IL-1β, the macrophage polarization markers nitric oxide synthase 2 (NOS2) (Mɸ1) and scavenging mannose receptor CD206 (Mɸ2), and the cell markers cluster of differentiation ( CD) 3 (T-cells), CD31 (endothelial cells), CD68 and CD163 (macrophages), were previously analysed as indicated [ 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Whether subcutaneous AT (SAT) reflects inflammatory activity in EAT and PAT, is not clear. We have shown that expression of nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related cytokines, to some degree, were mirrored in EAT, PAT and SAT [ 5 ]. A dysregulated or inflamed AT, often seen in obesity, is infiltrated by pro-inflammatory macrophages (M1mɸ) and other immune cells, resulting in a local production of cytokines [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD

Opstad,

Papotti,

Åkra

et al. 2023

J Transl Med

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Background Inflammation in cardiac adipose tissue (AT) is associated with atherosclerosis. We investigated whether the epicardial-, pericardial and pre-sternal subcutaneous AT (EAT, PAT and SAT) expression of Sirtuin1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) are involved in the inflammatory process in coronary heart disease (CHD), and potentially associated to nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers, macrophage polarization markers, cell markers and the cardiometabolic profile. Methods In this cohort study performed between 2016 and 2018, EAT, PAT and SAT biopsies were retrieved from 52 CHD patients (77% men, median age 67) undergoing open-chest coronary artery bypass grafting (CABG), and 22 patients (50% men, median age 69) undergoing aortic valve replacement serving as controls. AT samples were snap-frozen at – 80 °C until RNA extraction and AT expression of actual markers, relatively quantified by PCR. Circulating SIRT1 and NAMPT were measured with Enzyme-linked immunosorbent assays (ELISAs). Non-parametric statistical tests were mainly used, including Friedman’s test coupled to Wilcoxon signed-rank test and Spearman Correlation. Results SIRT1 and NAMPT levels were similar in CHD and controls. In CHD, SIRT1 and NAMPT were inter-correlated in all AT compartments (r = 0.37–0.56, p < 0.01, all), and differently expressed between compartments, with the highest expression in SAT, significantly different from EAT (p < 0.01, both). Circulating SIRT1 and NAMPT levels were inversely associated (r = − 0.32, p = 0.024). In EAT and SAT, SIRT1 expression was inversely associated with IL-18 (r = − 0.43 and r = − 0.38, p < 0.01, both), whereas NAMPT expression was positively associated with the NLRP3 inflammasome-related markers in all compartments (r = 0.37–0.55, p < 0.01, all). While SIRT1 and NAMPT correlated to nitric oxide synthase 2 (NOS2), especially in SAT (r = 0.50–0.52, p ≤ 0.01, both), SIRT1 expression was related to endothelial cells, and NAMPT to macrophages. SIRT1 levels were correlated to weight and waist (r = 0.32 and r = 0.38, p < 0.03, both) and inversely to triglycerides and glycated haemoglobin (HbA1c) (r = − 0.33–− 0.37, p < 0.03, all), the latter positively correlated to NAMPT concentration (r = 0.39, p = 0.010). Conclusion The study indicates that targeting SIRT1, with its anti-inflammatory properties, may be a novel anti-inflammatory strategy in preventing atherosclerosis and CHD progression. NAMPT may be an early player in AT inflammation, mediating/reflecting a pro-inflammatory state. Trial Registration: Registration: Clinicaltrials.gov ID: NCT02760914, registered the 5th of February 2016, http://clinicaltrials.gov/NCT02760914 Graphical Abstract

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Early diagnostic value of carotid artery ultrasound parameters combined with epicardial adipose layer thickness in coronary heart disease

Xu,

2024

World J Clin Cases

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BACKGROUND Coronary heart disease is associated with coronary atherosclerosis indicated by carotid intima-media thickness (CIMT) thickening and altered vascular elasticity. The epicardial adipose layer can secrete proinflammatory factors that promote the formation of coronary atherosclerosis. Thus, the epicardial fat layer thickness (EAT) may also predict coronary heart disease. AIM To determine the role of common carotid artery ultrasound parameters and EAT in the early diagnosis of coronary artery disease. METHODS Based on coronary angiography, patients with newly suspected coronary heart disease were divided into case (n = 107) and control (n = 41) groups. The carotid ultrasound parameters, including vascular stiffness (β), elastic coefficient (EP), pulse wave conduction velocity (PWV-β), CIMT, and EAT were compared between the case and control groups and among patients with different lesion numbers in the case group. Pearson correlation was used to evaluate the early diagnostic value of EAT, common carotid artery elasticity, and CIMT for coronary heart disease. RESULTS EP, β, PWV-β, CIMT, and EAT were significantly higher in the case group compared with the levels in the control group (all P < 0.001). In the case group, lesions were detected in one vessel in 34 patients, two vessels in 38 patients, and three vessels in 35 patients. Within the case group, β, EP, PWV-β, CIMT, and EAT levels significantly increased with an increased number of lesions (all P < 0.001). EAT positively correlated with β, EP, PWV-β, and CIMT (all P < 0.01). The area under the curve for diagnosing coronary heart disease using EAT combined with CIMT and carotid elasticity was 0.893, and the sensitivity and specificity were 0.890 and 0.837. CONCLUSION EAT correlated well with changes in carotid artery elasticity and CIMT in patients with coronary heart disease. The combination of EAT, carotid artery elasticity, and CIMT facilitates the early diagnosis of coronary heart disease.

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The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Cited by 3 publications

References 50 publications

Macrophage polarization markers in subcutaneous, pericardial, and epicardial adipose tissue are altered in patients with coronary heart disease

Macrophage polarization markers in subcutaneous, pericardial, and epicardial adipose tissue are altered in patients with coronary heart disease

Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD

Early diagnostic value of carotid artery ultrasound parameters combined with epicardial adipose layer thickness in coronary heart disease

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