Philadelphia, PA- There has been increasing research for and clinical use of biomarkers that integrate metabolic and inflammatory signals for defining the risk of atherosclerotic cardiovascular disease (CVD). In humans, resistin is a plasma protein that is expressed primarily in inflammatory cells. Recombinant resistin upregulates cytokines and the _expression of human endothelial cells, suggesting a potential role in atherosclerosis. Muredach P. Reilly et al, from the University of Pennsylvania Medical Center, published a study in the February 22, 2005 issue of Circulation indicating that plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans. 

The study examined whether plasma resistin levels were associated with metabolic and inflammatory markers, as well as with coronary artery calcification (CAC), which is a quantitative index of atherosclerosis. A total of 879 unrelated, asymptomatic, nondiabetic subjects were measured for resistin levels and inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNF-R2), and soluble intercellular adhesion molecule-1 (sol ICAM-1). Plasma C-reactive protein (CRP), lipoprotein-associated phopholipase A₂ (LpPLA₂) and insulin levels were also measured.  

Results showed resistin levels were positively associated with levels of inflammatory markers, including TNF-R2 (P<0.001), IL-6 (P<0.04) and LpPLA₂ (P=0.002). Resistin was not a measure of insulin resistance in multivariable analysis. Resistin levels were associated with increasing CAC after adjustment for age, sex and established risk factors (OR, 1.23 [CI, 1.03 to 1.52], P=0.03). A further adjustment for metabolic syndrome and CRP levels strengthened the association with CAC scores (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. In a sample of people with type 2 diabetes, there was a modest increase in resistin seen in overweight and type 2 diabetics.  

Plasma resistin levels are correlated with markers of inflammation and are predictive of coronary atherosclerosis in humans, independent of CRP. Resistin is a novel protein linked with both insulin resistance and inflammation. While in rodents, resistin is expressed in adipose tissue and regulates glucose metabolism and insulin sensitivity, in humans, resistin is detectable in inflammatory cells. Thus, resistin may be regulated by inflammatory signals. It is also important to note that obesity and type 2 diabetes are associated with activation of innate immune pathways and chronic inflammation, which may explain the increase in resistin in the sample of type 2 diabetics. Furthermore, recombinant resistin upregulates cytokines and the _expression of human endothelial cells, suggesting a potential role in atherosclerosis. The study indicates that further studies are needed to define the relationship of resistin to clinical cardiovascular disease. 

In conclusion, plasma levels of resistin were associated with inflammatory markers in a large, nondiabetic sample as well as in type 2 diabetes. Resistin was also associated with coronary atherosclerosis.  

Co-authors: Michael Lehrke, MD; Megan L. Wolfe, BS, Anand Rohatgi, MD; Mitchell A. Lazar, MD, PhD; Daniel J. Rader, MD.