Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators

Mazurek, Tomasz; Zhang, Lifeng; Zalewski, Andrew; Mannion, John D.; Diehl, James T.; Arafat, Hwyda A.; Sarov‐Blat, Lea; O’Brien, Shawn; Keiper, Elizabeth A.; Johnson, A. G.; Martin, Jack L.; Goldstein, Barry J.; Shi, Yi

doi:10.1161/01.cir.0000099542.57313.c5

Cited by 1,615 publications

(1,477 citation statements)

References 27 publications

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“…In obesity, infiltrating macrophages account for almost all TNF-α expression and a significant proportion of the expression of other inflammatory mediators in adipose tissue [6]. Interestingly, the epicardial adipose tissue of patients with CAD produces increased amounts of MCP-1, TNF-α, IL-1β, and IL-6 compared with epicardial adipose tissue of subjects without CAD, suggesting that regional adipose tissue may be a source of atherogenic proinflammatory molecules [39].…”

Section: Discussionmentioning

confidence: 99%

Association between the A?2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus

et al. 2004

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Aims/hypothesis. The molecular mechanisms of obesity-related insulin resistance are incompletely understood. Macrophages accumulate in adipose tissue of obese individuals. In obesity, monocyte chemoattractant protein-1 (MCP-1), a key chemokine in the process of macrophage accumulation, is overexpressed in adipose tissue. MCP-1 is an insulin-responsive gene that continues to respond to exogenous insulin in insulin-resistant adipocytes and mice. MCP-1 decreases insulin-stimulated glucose uptake into adipocytes. The A-2518G polymorphism in the distal regulatory region of MCP-1 may regulate gene expression. The aim of this study was to investigate the impact of this gene polymorphism on insulin resistance. Methods. We genotyped the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort (n=3307). Insulin resistance, estimated by homeostasis model assessment, and Type 2 diabetes were diagnosed in 803 and 635 patients respectively. Results. Univariate analysis revealed that plasma MCP-1 levels were significantly and positively correlated with WHR (p=0.011), insulin resistance (p=0.0097) and diabetes (p<0.0001). Presence of the MCP-1 G-2518 allele was associated with decreased plasma MCP-1 (p=0.017), a decreased prevalence of insulin resistance (odds ratio [OR]=0.82, 95% CI: 0.70-0.97, p=0.021) and a decreased prevalence of diabetes (OR=0.80, 95% CI: 0.67-0.96, p=0.014). In multivariate analysis, the G allele retained statistical significance as a negative predictor of insulin resistance (OR=0.78, p=0.0060) and diabetes (OR=0.80, p=0.018). Conclusions/interpretation. In a large cohort of Caucasians, the MCP-1 G-2518 gene variant was significantly and negatively correlated with plasma MCP-1 levels and the prevalence of insulin resistance and Type 2 diabetes. These results add to recent evidence supporting a role for MCP-1 in pathologies associated with hyperinsulinaemia.

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Section: Discussionmentioning

confidence: 99%

Association between the A?2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus

et al. 2004

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“…Several prospective epidemiological studies confirmed that inflammation might confer an increased risk of AF [10]. A previous study assessed inflammation of EAT that was harvested from patients undergoing cardiac surgery, and showed that it represented an important local source of the inflammatory mediators tumor necrosis factor-a and interleukin-6 [21,22], which might have direct arrhythmogenic effects on atrial tissue and be associated with AF pathogenesis [23].…”

Section: Inflammation Of Eat and Afmentioning

confidence: 99%

“…Chronic inflammation is not only associated with the presence of AF, but also predicts patients at increased risk of developing AF [10]. In CAD, the extent of EAT accumulation is associated with disease severity, and perivascular adipocytes are known to secrete inflammatory cytokines [4,[11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation

Kusayama

Furusho

Kashiwagi

et al. 2016

Journal of Cardiology

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“…Furthermore, MCP-1 mRNA was primarily found in the nonfat cells obtained by collagenase digestion of human adipose tissue rather than adipocytes and the addition of IL-1b or tumor necrosis factor a (TNFa) to isolated tissue explants incubated for 48 h in fresh medium after a prior overnight incubation-enhanced MCP-1 formation. 9 Mazurek et al 10 reported that the level of MCP-1 mRNA as well as secretion by human epicardial adipose tissue explants was greater than that seen in subcutaneous adipose tissue surrounding leg veins in patients undergoing elective coronary artery bypass surgery. Similar increases were seen in expression of other inflammatory markers such as IL-6, IL1b and TNFa in epicardial adipose tissue and attributed to the greater content of inflammatory cells such as macrophages, mast cells and T cells in epicardial as contrasted to subcutaneous fat.…”

Section: Introductionmentioning

confidence: 99%

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

Fain

Madan

2005

Int J Obes

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BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment during inflammation whose plasma level is elevated in obesity. OBJECTIVE: The present studies were designed to examine the release of MCP-1 in primary culture by explants of visceral adipose tissue from morbidly obese women. RESULTS: Most of the MCP-1 released by adipose tissue explants was derived from the nonfat cells in adipose tissue. The release of MCP-1 by adipose tissue explants was upregulated almost five-fold between 3 and 48 h of incubation. Approximately half of this upregulation was due to the release of endogenous tumor necrosis factor a (TNFa) and IL-1b based on the ability of a combination of a soluble TNFa receptor (etanercept) and a blocking antibody against IL-1b to reduce MCP-1 release. The release of MCP-1 over 48 h was unaffected by insulin or dexamethasone but significantly reduced by the combination of both agents. MCP-1 release was reduced by 60% in the presence of an inhibitor of the nuclear factor kB (NF-kB) pathway. There were no significant effects of inhibitors of p44/42 mitogen-activated protein kinase (ERK), Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK) pathways on MCP-1 release. However, inhibition of MCP-1 release in the presence of inhibitors of both the p38 MAPK and NF-kB pathways was greater than that seen with only the NF-kB inhibitor. DISCUSSION: The present data shows that MCP-1 formation is upregulated over a 48-h incubation of primary explants of visceral adipose tissue. Half of this upregulation is dependent upon endogenous TNFa and Il-1b and involves the p38 MAPK and NF-kB pathways.

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Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators

Cited by 1,615 publications

References 27 publications

Association between the A?2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus

Association between the A?2518G polymorphism in the monocyte chemoattractant protein-1 gene and insulin resistance and Type 2 diabetes mellitus

Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation

Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue

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