Journal of Endocrinological Investigation

, Volume 38, Issue 12, pp 1291–1299 | Cite as

Relation of resistin to proprotein convertase subtilisin–kexin type 9 levels in coronary artery disease patients with different nutritional status

  • S. Li
  • R. X. Xu
  • Y. Zhang
  • Y. L. Guo
  • C. G. Zhu
  • G. Liu
  • Q. Dong
  • J. J. Li
Original Article



To investigate the association of resistin with proprotein convertase subtilisin–kexin type 9 (PCSK9) levels, another novel regulator of atherosclerosis, in the condition of coronary artery disease (CAD).

Research design and methods

We prospectively enrolled a total of 356 consecutive stable CAD patients who were not treated with lipid-lowering drugs in the present study. The baseline clinical characteristics were collected. Plasma PCSK9 and resistin levels were determined by ELISA. The relationship between plasma PCSK9 and resistin levels was investigated.


Overall, plasma resistin exhibited a positive nonparametric correlation with PCSK9 levels (r = 0.123, p = 0.02). When the patients were classified into groups based on body mass index (BMI), the resistin correlated significantly to the PCSK9 levels in patients with BMI < 25 kg/m2 (r = 0.162, p = 0.026) but not in patients with BMI ≥ 25 kg/m2 (r = 0.087, p = 0.205). Multivariate regression analysis corroborated the relation between the PCSK9 and an elevated resistin level in patients with BMI < 25 kg/m2 independently of traditional parameters including age, sex, BMI, smoking, family history of CAD, systolic blood pressure, glucose, low density lipoprotein cholesterol, white blood cell, neutrophil to lymphocyte ratio, and high-sensitive C-reactive protein.


Plasma resistin was positively related to PCSK9 levels in CAD patients with normal weight, suggesting that the circulating resistin might represent a link with PCSK9 level variations in CAD progression of normal body weight.


Proprotein convertase subtilisin/kexin type 9 Resistin Coronary artery disease Obesity 



Coronary artery disease


Body mass index


Systolic blood pressure


Diastolic blood pressure


Total cholesterol


Low density lipoprotein cholesterol


High density lipoprotein cholesterol




White blood cell


Neutrophil to lymphocyte ratio


High-sensitive C-reactive protein


Proprotein convertase subtilisin/kexin type 9


  1. 1.
    Mendis S, Chestnov O (2014) The global burden of cardiovascular diseases: a challenge to improve. Curr Cardiol Rep 16(5):486CrossRefPubMedGoogle Scholar
  2. 2.
    Wang JC, Bennett M (2012) Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res 111(2):245–259CrossRefPubMedGoogle Scholar
  3. 3.
    van Diepen JA, Berbee JF, Havekes LM et al (2013) Interactions between inflammation and lipid metabolism: relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis 228(2):306–315CrossRefPubMedGoogle Scholar
  4. 4.
    Steppan CM, Bailey ST, Bhat S et al (2001) The hormone resistin links obesity to diabetes. Nature 409(6818):307–312CrossRefPubMedGoogle Scholar
  5. 5.
    Holcomb IN, Kabakoff RC, Chan B et al (2000) FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J 19(15):4046–4055PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    de Luis DA, Sagrado MG, Conde R et al (2010) Relation of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naive diabetes obese patients. Diabetes Res Clin Pract 89(2):110–114CrossRefPubMedGoogle Scholar
  7. 7.
    Melone M, Wilsie L, Palyha O et al (2012) Discovery of a new role of human resistin in hepatocyte low-density lipoprotein receptor suppression mediated in part by proprotein convertase subtilisin/kexin type 9. J Am Coll Cardiol 59(19):1697–1705CrossRefPubMedGoogle Scholar
  8. 8.
    Abifadel M, Varret M, Rabes JP et al (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156CrossRefPubMedGoogle Scholar
  9. 9.
    Lambert G, Charlton F, Rye KA et al (2009) Molecular basis of PCSK9 function. Atherosclerosis 203(1):1–7CrossRefPubMedGoogle Scholar
  10. 10.
    Stein EA, Raal FJ (2013) Insights into PCSK9, low-density lipoprotein receptor, and low-density lipoprotein cholesterol metabolism: of mice and man. Circulation 127(24):2372–2374CrossRefPubMedGoogle Scholar
  11. 11.
    Wu NQ, Li JJ (2014) PCSK9 gene mutations and low-density lipoprotein cholesterol. Clin Chim Acta 431:148–153CrossRefPubMedGoogle Scholar
  12. 12.
    Kwakernaak AJ, Lambert G, Dullaart RP (2012) Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects. Clin Biochem 45(16–17):1522–1524CrossRefPubMedGoogle Scholar
  13. 13.
    Hampton EN, Knuth MW, Li J et al (2007) The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain. Proc Natl Acad Sci 104(37):14604–14609PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Rashid S, Kastelein JJ (2013) PCSK9 and resistin at the crossroads of the atherogenic dyslipidemia. Expert Rev Cardiovasc Ther 11(11):1567–1577CrossRefPubMedGoogle Scholar
  15. 15.
    Li S, Guo YL, Xu RX et al (2014) Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis 234(2):441–445CrossRefPubMedGoogle Scholar
  16. 16.
    Li S, Guo YL, Xu RX et al (2014) Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis. Int J Cardiol 174:873–874CrossRefGoogle Scholar
  17. 17.
    Guo YL, Liu J, Xu RX et al (2013) Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9. Clin Drug Investig 33(12):877–883CrossRefPubMedGoogle Scholar
  18. 18.
    Li JJ, Nie SP, Qian XW et al (2009) Chronic inflammatory status in patients with coronary artery ectasia. Cytokine 46(1):61–64CrossRefPubMedGoogle Scholar
  19. 19.
    Hong LF, Li XL, Luo SH et al (2014) Relation of leukocytes and its subsets counts with the severity of stable coronary artery disease in patients with diabetic mellitus. PLoS ONE 9(3):e90663PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Baass A, Dubuc G, Tremblay M et al (2009) Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem 55(9):1637–1645CrossRefPubMedGoogle Scholar
  21. 21.
    Cariou B, Le May C, Costet P (2011) Clinical aspects of PCSK9. Atherosclerosis 216(2):258–265CrossRefPubMedGoogle Scholar
  22. 22.
    Steppan CM, Lazar MA (2004) The current biology of resistin. J Intern Med 255(4):439–447CrossRefPubMedGoogle Scholar
  23. 23.
    Bo S, Gambino R, Pagani A et al (2005) Relationships between human serum resistin, inflammatory markers and insulin resistance. Int J Obes (Lond) 29(11):1315–1320CrossRefGoogle Scholar
  24. 24.
    Shetty GK, Economides PA, Horton ES et al (2004) Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27(10):2450–2457CrossRefPubMedGoogle Scholar
  25. 25.
    Ohmori R, Momiyama Y, Kato R et al (2005) Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol 46(2):379–380CrossRefPubMedGoogle Scholar
  26. 26.
    Reilly MP, Lehrke M, Wolfe ML et al (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111(7):932–939CrossRefPubMedGoogle Scholar
  27. 27.
    Jamaluddin MS, Weakley SM, Yao Q et al (2012) Resistin: functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol 165(3):622–632PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Choi HY, Kim S, Yang SJ et al (2011) Association of adiponectin, resistin, and vascular inflammation: analysis with 18F-fluorodeoxyglucose positron emission tomography. Arterioscler Thromb Vasc Biol 31(4):944–949CrossRefPubMedGoogle Scholar
  29. 29.
    Urban D, Poss J, Bohm M et al (2013) Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 62(16):1401–1408CrossRefPubMedGoogle Scholar
  30. 30.
    Hotamisligil GS (2003) The irresistible biology of resistin. J Clin Invest 111(2):173–174PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  • S. Li
    • 1
  • R. X. Xu
    • 1
  • Y. Zhang
    • 1
  • Y. L. Guo
    • 1
  • C. G. Zhu
    • 1
  • G. Liu
    • 1
  • Q. Dong
    • 1
  • J. J. Li
    • 1
  1. 1.Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina

Personalised recommendations