Macrophage migration inhibitory factor is associated with vascular dysfunction in patients with end-stage renal disease

Int J Cardiol. 2013 Oct 15;168(6):5249-56. doi: 10.1016/j.ijcard.2013.08.021. Epub 2013 Aug 14.

Abstract

Background: Patients with end-stage renal disease (ESRD) show a high prevalence of cardiovascular disease with arterial stiffness, atherosclerosis and endothelial dysfunction, leading to increased morbidity and mortality. The cytokine macrophage migration inhibitory factor (MIF) exhibits proinflammatory and proatherogenic functions and has recently emerged as a major regulator of atherogenesis. Studies examining the relationship between circulating MIF levels and vascular dysfunction in this high-risk population do not exist.

Methods: In patients with ESRD (n = 39) and healthy controls (n = 16) we assessed endothelial function by flow-mediated dilation of the brachial artery and arterial stiffness (augmentation pressure, augmentation index and pulse pressure) using applanation tonometry. High-sensitive Troponin and subendocardial viability ratio were determined to assess myocardial injury.

Results: Patients with ESRD had impaired endothelial function and higher plasma MIF levels. MIF levels negatively correlated with endothelial function (r = -0.345, P = 0.031) and positively with arterial stiffness indices in patients with ESRD (pulse pressure r = -0.374, P = 0.019 and augmentation pressure r = -0.423, P = 0.025). In multivariate regression models besides age, gender, weight, and heart rate, MIF was an independent predictor for arterial stiffness. Impact on myocardial end-organ damage was reflected by correlation with high-sensitive Troponin I (r = 0.43, P = 0.009).

Conclusion: Our findings show that high MIF plasma levels are associated with diminished endothelial function and arterial stiffness and are correlated with myocardial injury. Further studies are necessary to investigate whether modulation of MIF might have an impact on atherosclerotic disease in this high-risk population.

Keywords: End-stage renal disease; Endothelial dysfunction; Macrophage migration inhibitory factor; Vascular stiffness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / epidemiology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / physiopathology
  • Biomarkers / blood
  • Blood Pressure / physiology
  • Cross-Sectional Studies
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / physiopathology
  • Macrophage Migration-Inhibitory Factors / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prevalence
  • Risk Factors
  • Troponin / blood
  • Vascular Stiffness / physiology
  • Vasodilation / physiology

Substances

  • Biomarkers
  • Macrophage Migration-Inhibitory Factors
  • Troponin
  • Intramolecular Oxidoreductases
  • MIF protein, human