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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    ABSTRACT: Abdominal obesity is associated with insulin resistance and metabolic syndrome. However, specific contributions of distinct adipose tissue (AT) depots to metabolic complications of obesity are still unclear. In this study, the inflammatory profile of four distinct abdominal AT-depots and the relation between AT-characteristics and obesity-induced metabolic complications was evaluated. In 28 men undergoing abdominal aortic surgery, biopsies were collected from subcutaneous fat (SAT), and 3 visceral AT-depots: mesenteric (MAT), omental (OAT) and periaortic (PAT). The AT biopsies were characterized morphologically (adipocyte size, capillary density, CD68 + macrophages and crown-like-structures (CLS)) and the ex vivo adipokine secretion profile was determined by multiplex-immunoassay. The relation between depot-specific inflammatory characteristics and clinical parameters (waist circumference, insulin resistance and metabolic syndrome) was assessed by multivariable linear regression analysis. PAT contained the smallest adipocytes, highest capillary density and secreted abundant amounts of adipokines. SAT contained the lowest amount of macrophages and adipokines, while MAT and OAT displayed a similar inflammatory profile. In contrast to the other depots, MAT inflammation was most strongly related to metabolic complications of obesity, as adipocyte size and CLS were related to insulin resistance (β2.0; 95%CI1.15-2.85 and β0.24; 95%CI0.06-0.43) and MAT adipocyte size was associated with 79% higher odds of having metabolic syndrome (OR1.79; 95% CI1.13-2.89). There are significant differences in the inflammatory profile of distinct abdominal fat depots, of which MAT characteristics were mostly associated with metabolic complications of obesity. These findings suggest a differential contribution of AT-depots to systemic metabolic dysfunction which precedes type 2 diabetes and vascular diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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    ABSTRACT: Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality. Diabetic foot syndrome (DFS), as defined by the World Health Organization, is an "ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection". Pathogenic events able to cause diabetic foot ulcers are multifactorial. Among the commonest causes of this pathogenic pathway it's possible to consider peripheral neuropathy, foot deformity, abnormal foot pressures, abnormal joint mobility, trauma, peripheral artery disease. Several studies reported how diabetic patients show a higher mortality rate compared to patients without diabetes and in particular these studies under filled how cardiovascular mortality and morbidity is 2-4 times higher among patients affected by type 2 diabetes mellitus. This higher degree of cardiovascular morbidity has been explained as due to the observed higher prevalence of major cardiovascular risk factor, of asymptomatic findings of cardiovascular diseases, and of prevalence and incidence of cardiovascular and cerebrovascular events in diabetic patients with foot complications. In diabetes a fundamental pathogenic pathway of most of vascular complications has been reported as linked to a complex interplay of inflammatory, metabolic and procoagulant variables. These pathogenetic aspects have a direct interplay with an insulin resistance, subsequent obesity, diabetes, hypertension, prothrombotic state and blood lipid disorder. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects as reported by Tuttolomondo et al confirmed the pathogenetic issue of the a "adipo-vascular" axis that may contribute to cardiovascular risk in patients with type 2 diabetes. This "adipo-vascular axis" in patients with type 2 diabetes has been reported as characterized by lower plasma levels of adiponectin and higher plasma levels of interleukin-6 thus linking foot ulcers pathogenesis to microvascular and inflammatory events. The purpose of this review is to highlight the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients and to focus the management of major complications related to diabetes such as infections and peripheral arteriopathy.

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