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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAtherosclerosis is recognized as a complex inflammatory condition in which various immune system cells interact with each other and with cells of the arterial wall. This article describes inflammation as the underlying mechanism that links obesity and atherosclerosis.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiometabolic Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/2\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-98463152\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/2\/4\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/2\/4\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/2\/4\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12250\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-2\u0022\u003EJust a few decades ago, atherosclerosis was viewed as a lipid storage disease, in which cholesterol accumulated as a waxy deposit within the walls of an inanimate artery, similar to rust clogging a pipe. Today, atherosclerosis is recognized as a complex inflammatory condition in which various immune system cells interact with each other and with cells of the arterial wall. Peter Libby, MD, Harvard Medical School, Boston, Massachusetts, USA, described inflammation as the underlying mechanism that links obesity and atherosclerosis.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENatural History of Atherosclerosis\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EWithin normal blood vessels in homeostasis, inflammatory cells are not typically present at the vessel wall. But when the vessel endothelium is exposed to atherogenic stimuli, such as dyslipidemia, diabetes, and hypertension, endothelial cells express adhesion molecules that attract leukocytes. In response to chemoattractant messages, leukocytes adhere to the vessel wall and enter the arterial intima. Monocytes are recruited in the largest number among all leukocytes. In the presence of hyperlipidemia, monocytes propagate the innate immune response by expressing proinflammatory cytokines and differentiating into proinflammatory macrophages.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EMonocyte-derived macrophages absorb modified lipoproteins to become foam cells, the characteristic cells of the initial atherosclerotic lesion [Libby P et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2007]. Other cells of the innate immune response, including mast cells, also are recruited through proinflammatory signaling to participate in atherogenesis.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EInnate Immunity and Atherosclerosis\u003C\/h2\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EAdipose tissue is a source of cytokines that mediate systemic inflammation, insulin resistance, and endothelial dysfunction, all of which promote atherosclerosis. Adipose tissue macrophages mediate some of the inflammatory changes that are characteristic of obesity. Two distinct populations of macrophages have been identified within adipose tissue. Proinflammatory macrophages, which are more predominant in visceral adipose tissue, secrete inflammatory cytokines, such as tumor necrosis factor (TNF) and inducible nitric oxide synthase (iNOS). Anti-inflammatory macrophages secrete anti-inflammatory cytokines that quell inflammation and facilitate tissue repair [Rocha VZ et al. \u003Cem\u003ENat Rev Cardiol\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EImaging studies have been instrumental in demonstrating the metabolic differences between visceral and subcutaneous adipose tissue. As body weight increases, proinflammatory macrophages accumulate in visceral adipose tissue. In a study of adipose tissue in mice that consumed a high-fat diet, obesity that was associated with increased expression of TNF and iNOS rose, indicating enhanced activity of proinflammatory macrophages [Lumeng CN et al. \u003Cem\u003EJ Clin Invest\u003C\/em\u003E 2007]. Using whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans, Dr. Libby and colleagues showed that glucose uptake is significantly greater in macrophage-rich visceral adipose tissue compared with subcutaneous adipose tissue [Christen T et al. \u003Cem\u003EJ Am Coll Cardiol Img\u003C\/em\u003E 2010].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EAdaptive Immunity and Atherosclerosis\u003C\/h2\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EObesity is associated with increased accumulation of T cells in adipose tissue. Recent research suggests that T cells play an important role in modulating the immune response to atherogenesis. T cells enter arterial plaque by interacting with adhesion molecules on the surface of endothelial cells, in response to chemoattractants, such as regulated on activation, normal T cell expressed and secreted (RANTES) [Wu H et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EOnce in the vessel wall, type 1 helper T (Th1) cells can induce proinflammatory responses in macrophages by releasing interferon (IFN)-gamma [Nishimura S et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2009; Rocha VZ et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2008]. Another population of regulatory T cells, type 2 helper T (Th2) cells, produces interleukin (IL)-4 and IL-13. These cytokines attenuate many of the highly proinflammatory effects of IFN-gamma. Therefore, through the proinflammatory effects of IFN-gamma and the anti-inflammatory effects of IL-4 and IL-13, T lymphocytes regulate signals that promote the accumulation of macrophages within visceral adipose tissue [Rocha VZ et al. \u003Cem\u003ENat Rev Cardiol\u003C\/em\u003E 2009].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EClinical Implications and New Therapeutic Opportunities\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EClinicians now understand that obesity, inflammation, and atherosclerosis are closely linked. Visceral fat accumulation contributes to the systemic inflammation that drives atherosclerosis and its complications, including arterial stenosis and thrombosis. Within atherosclerotic plaques, increased activation of inflammatory cells promotes thrombosis and increases the risk of acute coronary syndromes. Recognizing these pathways opens up new possibilities for therapy, including a new focus on anti-inflammatory therapies for the management of atherosclerosis.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003ENew options for risk assessment are also available. For instance, biomarkers, such as high-sensitivity C-reactive protein (hsCRP), are emerging as important markers of systemic inflammation. In patients with diabetes, elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in blood and in the arterial wall may favor decreased fibrinolysis and accelerated atherosclerosis [Calles-Escandon J et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 1998; Pandolfi A et al. \u003Cem\u003EArterioscler Thromb Vasc Biol\u003C\/em\u003E 2001]. After adjusting for body mass index (BMI), hsCRP correlates with abdominal visceral adiposity. In addition, hsCRP levels predict cardiovascular events in apparently healthy persons and in those with manifest atherosclerotic disease, independently of traditional risk factors. Inflammatory biomarkers can guide the use of statins and perhaps other therapies that modify systemic inflammation in patients with atherosclerosis.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/2\/4.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn3mq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn3mq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}