February 23, 2005
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
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.
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.
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.
Lehrke, MD; Megan L. Wolfe, BS, Anand Rohatgi, MD; Mitchell A.
Lazar, MD, PhD; Daniel J. Rader, MD.