Resistin is an inflammatory marker of atherosclerosis in humans

Division of Cardiology, Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pa, USA. .
Circulation (Impact Factor: 14.95). 03/2005; 111(7):932-9. DOI: 10.1161/01.CIR.0000155620.10387.43
Source: PubMed

ABSTRACT Resistin, a plasma protein, induces insulin resistance in rodents. Recent reports suggest that circulating levels of resistin are elevated in obese and insulin-resistant rodents and humans. Whereas rodent resistin is made in adipocytes, macrophages are a major source of human resistin. Given the convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and atherosclerosis in humans.
We examined whether plasma resistin levels were associated with metabolic and inflammatory markers, as well as with coronary artery calcification (CAC), a quantitative index of atherosclerosis, in 879 asymptomatic subjects in the Study of Inherited Risk of Coronary Atherosclerosis. Resistin levels were positively associated with levels of inflammatory markers, including soluble tumor necrosis factor-alpha receptor-2 (P<0.001), interleukin-6 (P=0.04), and lipoprotein-associated phospholipase A2 (P=0.002), but not measures of insulin resistance in multivariable analysis. Resistin levels also were associated (odds ratio and 95% confidence interval in ordinal regression) with increasing CAC after adjustment for age, sex, and established risk factors (OR, 1.23 [CI, 1.03 to 1.52], P=0.03) and further control for metabolic syndrome and plasma C-reactive protein (CRP) levels (OR, 1.25 [CI, 1.04 to 1.50], P=0.01). In subjects with metabolic syndrome, resistin levels further predicted CAC, whereas CRP levels did not.
Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans, independent of CRP. Resistin may represent a novel link between metabolic signals, inflammation, and atherosclerosis. Further studies are needed to define the relationship of resistin to clinical cardiovascular disease.

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Available from: Anand Rohatgi, Feb 12, 2014
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    • "More recent studies have shown the causative association between resistin and systemic inflammation [19] [20], especially in the vascular endothelium [21]. From the viewpoint of inflammation, it is notable that plasma resistin concentrations increase with increasing inflammatory mediator levels predicting the severity of coronary atherosclerosis [22] also, Axelsson et al. (2006) concluded that the serum level of resistin was higher in patients with CKD [23]. "
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    ABSTRACT: Obstructive sleep apnea (OSA) has been independently associated with cardiovascular diseases, including hypertension, coronary heart disease and heart failure. Also, it had a deleterious impact on renal function and a link to diabetes mellitus (DM) and insulin resistance. Resistin is new adipokine and may play a role in cardiac, diabetics and renal patients.
    01/2015; 25(1). DOI:10.1016/j.ejcdt.2014.12.002
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    • "Prior studies have shown resistin to be linked to both endothelial and cardiomyocyte dysfunction, as well as alterations in cholesterol metabolism. Accordingly, the association of resistin with subclinical atherosclerosis has been illustrated by its relationship to elevated coronary artery calcium levels [11] and increased carotid intima-media thickness [37]. "
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    ABSTRACT: Objective: To describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort. Methods and results: We studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3, 1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes. Conclusions: In an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 239(1):101-108. DOI:10.1016/j.atherosclerosis.2014.12.044 · 3.97 Impact Factor
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    • "Circulating levels of inflammatory cytokines such as TNFa [24], IL6 [25], IL8 [26], IL1 [27], IL18 [28], SAA1 [25], leptin [29] and resistin [30] are potent predictors of adverse cardiovascular outcomes. Adipose tissue cytokines mainly act as autacoids in the fat compartment. "
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    ABSTRACT: Background and Aims Pro-inflammatory molecules produced by adipose tissue have been implicated in the risk of cardiovascular (CV) disease in obesity. We investigated the expression profile of 19 pro-inflammatory and 7 anti-inflammatory genes in subcutaneous adipose tissue (SAT) and in visceral adipose tissue (VAT) in 44 severely obese individuals who underwent bariatric surgery. Methods and Results SAT and VAT expressed an identical series of pro-inflammatory genes. Among these genes, twelve were significantly more expressed in SAT than in VAT while just one (IL18) was more expressed in VAT. The remaining genes were equally expressed. Among pro-inflammatory cytokines, both IL6 and IL8 were about 20 times more intensively expressed in SAT than in VAT. The expression of nine genes was highly associated in SAT and VAT. Only for 3 pro-inflammatory cytokines (IL8, IL18, SAA1) in SAT the gene expression in adipose tissue associated with the circulating levels of the corresponding gene products while no such an association was found as for VAT. Conclusions The expression of critical pro-inflammatory genes is substantially higher in SAT than in VAT in individuals with morbid obesity. The variability in circulating levels of pro-inflammatory cytokines is, in small part and just for three pro-inflammatory cytokines, explained by underlying gene expression in SAT but not in VAT. These results point to a compartment-specific adipose tissue contribution to inflammation in obesity and indicate that abdominal SAT contributes more than VAT to the pro-inflammatory milieu associated with severe obesity.
    Nutrition Metabolism and Cardiovascular Diseases 10/2014; 24(10). DOI:10.1016/j.numecd.2014.04.017 · 3.88 Impact Factor
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