Monocyte heterogeneity in obesity and subclinical atherosclerosis

Department of Internal Medicine IV, Saarland University Hospital, Homburg 66421, Germany.
European Heart Journal (Impact Factor: 15.2). 09/2009; 31(3):369-76. DOI: 10.1093/eurheartj/ehp308
Source: PubMed


AimsMonocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis.Methods and resultsWe assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14++CD16- and CD16+ cells, which we further subdivided into CD14++CD16+ and CD14 (+)CD16+ cells. Body mass index was significantly correlated with carotid IMT. High CD16+ monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16+ monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16+ monocyte numbers in obesity may partly explain the association between obesity and IMT.Conclusion
Our results reveal a significant univariate association between CD16+ monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16 + monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.

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    • "High levels of the CD14+CD16+ subset of CD16+ were associated with cardiovascular events [67] and reduced survival at 35 months in CKD patients [68]. In the same time, CD14dimCD16+ subtype was positively correlated with the BMI [65] and atherogenic lipoproteins and inversely associated with high-density lipoprotein cholesterol. "
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    ABSTRACT: Adipose tissue inflammation mediates the association between excessive body fat accumulation and several chronic inflammatory diseases. A high prevalence of obesity-associated adipose tissue inflammation was observed not only in patients with cardiovascular conditions but also in patients with inflammatory bowel diseases, abdominal aortic aneurysm, or cardiorenal syndrome. In addition to excessive caloric intake, other triggers promote visceral adipose tissue inflammation followed by chronic, low-grade systemic inflammation. The infiltration and accumulation of immune cells in the inflamed and hypertrophied adipose tissue promote the production of inflammatory cytokines, contributing to target organ damages. This comorbidity seems to delimit subgroups of individuals with systemic adipose tissue inflammation and more severe chronic inflammatory diseases that are refractory to conventional treatment. This review highlights the association between adipose tissue immune response and the pathophysiology of visceral adiposity-related chronic inflammatory diseases, while suggesting several new therapeutic strategies.
    Inflammation 05/2014; 37(4). DOI:10.1007/s10753-014-9914-1 · 2.21 Impact Factor
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    • "Moreover, circulating CD16+ monocyte levels are positively correlated with levels of atherogenic lipids [26] and plaque vulnerability [27], whereas it is negatively correlated with cardiac function such as left ventricular (LV) ejection fraction after AMI [28]. Significant increases in CD16+ monocyte levels have been described in human chronic pathologies in obesity as well [29]. In the same study, several groups reported differential expression of CD14dim and CD14high within CD16+ monocytes [26,30], which was related to distinct functional properties of the chemokine receptor expression pattern [31]. "
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    ABSTRACT: Monocytes express various receptors, which monitor and sense environmental changes. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Monocytes can differentiate into inflammatory or anti-inflammatory subsets. Upon tissue damage or infection, monocytes are rapidly recruited to the tissue, where they can differentiate into tissue macrophages or dendritic cells. Given the rapid progress in monocyte research from broad spectrum of inflammatory diseases, there is a need to summarize our knowledge in monocyte heterogeneity and its impact in human disease. In this review, we describe the current understanding of heterogeneity of human and murine monocytes, the function of distinct subsets of monocytes, and a potential mechanism for monocyte differentiation. We emphasize that inflammatory monocyte subsets are valuable biomarkers for inflammatory diseases, including cardiovascular diseases.
    01/2014; 2(1):1. DOI:10.1186/2050-7771-2-1
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    • "High CD16(+) monocyte counts were signi�cantly associated with both higher BMI Scienti�ca and increased carotid IMT. Adjustment for CD16(+) monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16(+) monocyte numbers in obesity may partly explain the association between obesity and IMT [40] "
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    ABSTRACT: Obesity has significant implications for healthcare, since it is a major risk factor for both type 2 diabetes and the metabolic syndrome. This syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. It is associated with high atherosclerotic cardiovascular risk, which can only partially be explained by its components. Therefore, to explain how obesity contributes to the development of metabolic and cardiovascular disorders, more and better insight is required into the effects of personal and environmental stress on disease processes. In this paper, we show that obesity is a chronic inflammatory disease, which has many molecular mechanisms in common with atherosclerosis. Furthermore, we focus on the role of oxidative stress associated with obesity in the development of the metabolic syndrome. We discuss how several stress conditions are related to inflammation and oxidative stress in association with obesity and its complications. We also emphasize the relation between stress conditions and the deregulation of epigenetic control mechanisms by means of microRNAs and show how this impairment further contributes to the development of obesity, closing the vicious circle. Finally, we discuss the limitations of current anti-inflammation and antioxidant therapy to treat obesity.
    12/2012; 2012:205027. DOI:10.6064/2012/205027
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