Resistin is an inflammatory marker of atherosclerosis in humans

Muredach P. Reilly, Michael Lehrke, Megan L. Wolfe, Anand Rohatgi, Mitchell A. Lazar, Daniel J. Rader

Research output: Contribution to journalArticle

698 Citations (Scopus)

Abstract

Background - 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. Methods and Results - 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-α 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. Conclusions - 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.

Original languageEnglish (US)
Pages (from-to)932-939
Number of pages8
JournalCirculation
Volume111
Issue number7
DOIs
StatePublished - Feb 22 2005

Fingerprint

Resistin
Atherosclerosis
C-Reactive Protein
Rodentia
Coronary Vessels
Inflammation
Adipocytes
Insulin Resistance
Blood Proteins
Coronary Artery Disease
1-Alkyl-2-acetylglycerophosphocholine Esterase
Macrophages
Receptors, Tumor Necrosis Factor, Type II
Interleukin-6
Cardiovascular Diseases
Obesity
Odds Ratio

Keywords

  • Atherosclerosis
  • Diabetes
  • Inflammation
  • Resistin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Reilly, M. P., Lehrke, M., Wolfe, M. L., Rohatgi, A., Lazar, M. A., & Rader, D. J. (2005). Resistin is an inflammatory marker of atherosclerosis in humans. Circulation, 111(7), 932-939. https://doi.org/10.1161/01.CIR.0000155620.10387.43

Resistin is an inflammatory marker of atherosclerosis in humans. / Reilly, Muredach P.; Lehrke, Michael; Wolfe, Megan L.; Rohatgi, Anand; Lazar, Mitchell A.; Rader, Daniel J.

In: Circulation, Vol. 111, No. 7, 22.02.2005, p. 932-939.

Research output: Contribution to journalArticle

Reilly, MP, Lehrke, M, Wolfe, ML, Rohatgi, A, Lazar, MA & Rader, DJ 2005, 'Resistin is an inflammatory marker of atherosclerosis in humans', Circulation, vol. 111, no. 7, pp. 932-939. https://doi.org/10.1161/01.CIR.0000155620.10387.43
Reilly, Muredach P. ; Lehrke, Michael ; Wolfe, Megan L. ; Rohatgi, Anand ; Lazar, Mitchell A. ; Rader, Daniel J. / Resistin is an inflammatory marker of atherosclerosis in humans. In: Circulation. 2005 ; Vol. 111, No. 7. pp. 932-939.
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AU - Reilly, Muredach P.

AU - Lehrke, Michael

AU - Wolfe, Megan L.

AU - Rohatgi, Anand

AU - Lazar, Mitchell A.

AU - Rader, Daniel J.

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N2 - Background - 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. Methods and Results - 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-α 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. Conclusions - 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.

AB - Background - 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. Methods and Results - 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-α 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. Conclusions - 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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