Circulation. 2005;111:932-939
Published online before print February 14, 2005, doi: 10.1161/01.CIR.0000155620.10387.43
Published online before print February 14, 2005, doi: 10.1161/01.CIR.0000155620.10387.43
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2005;111:932-939.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Resistin Is an Inflammatory Marker of Atherosclerosis in Humans
From the Divisions of Cardiology (M.P.R., D.J.R.) and Endocrinology, Diabetes, and Metabolism (M.L., M.A.L.), Department of Medicine (M.P.R., M.L., M.L.W., A.R., M.A.L., D.J.R.), Center for Experimental Therapeutics, and the Penn Diabetes Center (M.P.R., M.L.W., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
Correspondence to Muredach Reilly, Cardiovascular Division, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Blvd, Philadelphia, PA 19104-6160. E-mail muredach{at}spirit.gcrc.upenn.edu
Received November 5, 2004; accepted November 15, 2004.
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-
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.
Key Words: resistin • inflammation • diabetes • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  A. Qasim, N. N. Mehta, M. G. Tadesse, M. L. Wolfe, T. Rhodes, C. Girman, and M. P. Reilly Adipokines, insulin resistance, and coronary artery calcification. J. Am. Coll. Cardiol., July 15, 2008; 52(3): 231 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Weikert, S. Westphal, K. Berger, J. Dierkes, M. Mohlig, J. Spranger, E. B. Rimm, S. N. Willich, H. Boeing, and T. Pischon Plasma Resistin Levels and Risk of Myocardial Infarction and Ischemic Stroke J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2647 - 2653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Ahima and M. A. Lazar Adipokines and the Peripheral and Neural Control of Energy Balance Mol. Endocrinol., May 1, 2008; 22(5): 1023 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F. Chehab Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect? Endocrinology, March 1, 2008; 149(3): 925 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Ohman, Y. Shen, C. I. Obimba, A. P. Wright, M. Warnock, D. A. Lawrence, and D. T. Eitzman Visceral Adipose Tissue Inflammation Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, February 12, 2008; 117(6): 798 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takata, H. Osawa, M. Kurata, M. Kurokawa, J. Yamauchi, M. Ochi, W. Nishida, T. Okura, J. Higaki, and H. Makino Hyperresistinemia Is Associated With Coexistence of Hypertension and Type 2 Diabetes Hypertension, February 1, 2008; 51(2): 534 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Golledge, P. Clancy, K. Jamrozik, and P. E. Norman Obesity, Adipokines, and Abdominal Aortic Aneurysm: Health in Men Study Circulation, November 13, 2007; 116(20): 2275 - 2279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ellington, A. R. Malik, G. G. Klee, S. T. Turner, A. D. Rule, T. H. Mosley Jr, and I. J. Kullo Association of Plasma Resistin With Glomerular Filtration Rate and Albuminuria in Hypertensive Adults Hypertension, October 1, 2007; 50(4): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Beauloye, F. Zech, H. Tran Thi Mong, P. Clapuyt, M. Maes, and S. M. Brichard Determinants of Early Atherosclerosis in Obese Children and Adolescents J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3025 - 3032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Qatanani and M. A. Lazar Mechanisms of obesity-associated insulin resistance: many choices on the menu Genes & Dev., June 15, 2007; 21(12): 1443 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Knudson, G. M. Dick, and J. D. Tune Adipokines and Coronary Vasomotor Dysfunction Experimental Biology and Medicine, June 1, 2007; 232(6): 727 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ribatti, M. T. Conconi, and G. G. Nussdorfer Nonclassic Endogenous Novel Regulators of Angiogenesis Pharmacol. Rev., June 1, 2007; 59(2): 185 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Anderson, N. N. Mehta, M. L. Wolfe, C. C. Hinkle, L. Pruscino, L. L. Comiskey, J. Tabita-Martinez, K. F. Sellers, M. R. Rickels, R. S. Ahima, et al. Innate Immunity Modulates Adipokines in Humans J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2272 - 2279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Osawa, Y. Tabara, R. Kawamoto, J. Ohashi, M. Ochi, H. Onuma, W. Nishida, K. Yamada, J. Nakura, K. Kohara, et al. Plasma Resistin, Associated With Single Nucleotide Polymorphism -420, Is Correlated With Insulin Resistance, Lower HDL Cholesterol, and High-Sensitivity C-Reactive Protein in the Japanese General Population Diabetes Care, June 1, 2007; 30(6): 1501 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Musaad and E. N. Haynes Biomarkers of Obesity and Subsequent Cardiovascular Events Epidemiol. Rev., May 10, 2007; (2007) mxm005v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fantuzzi and T. Mazzone Adipose Tissue and Atherosclerosis: Exploring the Connection Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 996 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Kadoglou, D. Perrea, F. Iliadis, N. Angelopoulou, C. Liapis, and M. Alevizos Exercise Reduces Resistin and Inflammatory Cytokines in Patients With Type 2 Diabetes Diabetes Care, March 1, 2007; 30(3): 719 - 721. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bertolani, P. Sancho-Bru, P. Failli, R. Bataller, S. Aleffi, R. DeFranco, B. Mazzinghi, P. Romagnani, S. Milani, P. Gines, et al. Resistin as an Intrahepatic Cytokine: Overexpression during Chronic Injury and Induction of Proinflammatory Actions in Hepatic Stellate Cells Am. J. Pathol., December 1, 2006; 169(6): 2042 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Dick, P. S. Katz, M. Farias III, M. Morris, J. James, J. D. Knudson, and J. D. Tune Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2997 - H3002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kremen, M. Dolinkova, J. Krajickova, J. Blaha, K. Anderlova, Z. Lacinova, D. Haluzikova, L. Bosanska, M. Vokurka, S. Svacina, et al. Increased Subcutaneous and Epicardial Adipose Tissue Production of Proinflammatory Cytokines in Cardiac Surgery Patients: Possible Role in Postoperative Insulin Resistance J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4620 - 4627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Park, S. S. Choe, A H. Choi, K. H. Kim, M. J. Yoon, T. Suganami, Y. Ogawa, and J. B. Kim Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals Diabetes, November 1, 2006; 55(11): 2939 - 2949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qi, Z. Nie, Y.-S. Lee, N. S. Singhal, P. E. Scherer, M. A. Lazar, and R. S. Ahima Loss of Resistin Improves Glucose Homeostasis in Leptin Deficiency Diabetes, November 1, 2006; 55(11): 3083 - 3090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ghanim, S. Dhindsa, A. Aljada, A. Chaudhuri, P. Viswanathan, and P. Dandona Low-Dose Rosiglitazone Exerts an Antiinflammatory Effect with an Increase in Adiponectin Independently of Free Fatty Acid Fall and Insulin Sensitization in Obese Type 2 Diabetics J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3553 - 3558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Otero, R Lago, R Gomez, F Lago, C Dieguez, J J Gomez-Reino, and O Gualillo Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis Ann Rheum Dis, September 1, 2006; 65(9): 1198 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bahr, J. Ockenga, K. H. W. Boker, M. P. Manns, and U. J. F. Tietge Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E199 - E206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kunnari, O. Ukkola, M. Paivansalo, and Y. A. Kesaniemi High Plasma Resistin Level Is Associated with Enhanced Highly Sensitive C-Reactive Protein and Leukocytes J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2755 - 2760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Menzaghi, A. Coco, L. Salvemini, R. Thompson, S. De Cosmo, A. Doria, and V. Trischitta Heritability of Serum Resistin and Its Genetic Correlation with Insulin Resistance-Related Features in Nondiabetic Caucasians J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2792 - 2795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nigro, N. Osman, A. M. Dart, and P. J. Little Insulin Resistance and Atherosclerosis Endocr. Rev., May 1, 2006; 27(3): 242 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Mu, R. Ohashi, S. Yan, H. Chai, H. Yang, P. Lin, Q. Yao, and C. Chen Adipokine resistin promotes in vitro angiogenesis of human endothelial cells Cardiovasc Res, April 1, 2006; 70(1): 146 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Kim, O. H. Ryu, H. Y. Kim, K. W. Lee, J. A Seo, N. H. Kim, K. M. Choi, J. Lee, S. H. Baik, and D. S. Choi Effect of rosiglitazone on plasma adiponectin levels and arterial stiffness in subjects with prediabetes or non-diabetic metabolic syndrome. Eur. J. Endocrinol., March 1, 2006; 154(3): 433 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Samaha, P. O. Szapary, N. Iqbal, M. M. Williams, L. T. Bloedon, A. Kochar, M. L. Wolfe, and D. J. Rader Effects of Rosiglitazone on Lipids, Adipokines, and Inflammatory Markers in Nondiabetic Patients With Low High-Density Lipoprotein Cholesterol and Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 624 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Burnett, J. M. Devaney, R. J. Adenika, R. Lindsay, and B. V. Howard Cross-Sectional Associations of Resistin, Coronary Heart Disease, and Insulin Resistance J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 64 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Szapary, L. T. Bloedon, F. F. Samaha, D. Duffy, M. L. Wolfe, D. Soffer, M. P. Reilly, J. Chittams, and D. J. Rader Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 182 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann Large meals and large arteries: Is resistin the link? Cardiovasc Res, January 1, 2006; 69(1): 9 - 12. [Full Text] [PDF]
|
|
|
|
|
|
H. S. Jung, K.-H. Park, Y. M. Cho, S. S. Chung, H. J. Cho, S. Y. Cho, S. J. Kim, S. Y. Kim, H. K. Lee, and K. S. Park Resistin is secreted from macrophages in atheromas and promotes atherosclerosis Cardiovasc Res, January 1, 2006; 69(1): 76 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden 2nd International Symposium on Triglycerides and HDL: Metabolic syndrome Diabetes Care, October 1, 2005; 28(10): 2577 - 2584. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Graveleau, V. G. Zaha, A. Mohajer, R. R. Banerjee, N. Dudley-Rucker, C. M. Steppan, M. W. Rajala, P. E. Scherer, R. S. Ahima, M. A. Lazar, et al. Mouse and Human Resistins Impair Glucose Transport in Primary Mouse Cardiomyocytes, and Oligomerization Is Required for This Biological Action J. Biol. Chem., September 9, 2005; 280(36): 31679 - 31685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kamin, C. Hadigan, M. Lehrke, S. Mazza, M. A. Lazar, and S. Grinspoon Resistin Levels in Human Immunodeficiency Virus-Infected Patients with Lipoatrophy Decrease in Response to Rosiglitazone J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3423 - 3426. [Abstract] [Full Text] [PDF]
|
|