Plasma biomarkers of endothelial dysfunction in patients with hypertrophic cardiomyopathy

Pharmacol Rep. 2007 Nov-Dec;59(6):715-20.

Abstract

Impairment of endothelium-dependent coronary vasodilatation has been reported in hypertrophic cardiomyopathy (HCM). The aim of our study was to evaluate whether HCM patients have increased circulating blood markers of endothelial dysfunction. We compared 29 HCM patients with sinus rhythm, including 11 with the left ventricular outflow tract (LVOT) obstruction (gradient > 30 mmHg), versus 29 age- and sex-matched controls without cardiovascular diseases. Plasma levels of the following endothelial biomarkers were determined: soluble thrombomodulin (sTM), von Willebrand factor (vWF), tissue factor pathway inhibitor (TFPI), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDAM) and L-arginine to ADMA (Arg/ADMA) ratio. Both sTM (49.1 +/- 9.9 vs. 39.1 +/- 4.8 ng/ml, p < 0.00001) and TFPI (18.6 +/- 2.5 vs. 16.2 +/- 1.7 ng/ml, p < 0.0001) were elevated in HCM patients compared with controls, whereas vWF levels were similar in both groups (105.8 +/- 11.6 vs. 102.2 +/- 10.9 U/dl, p > 0.05). Among markers related to the nitric oxide pathways, we observed elevations of both ADMA (0.57 +/- 0.08 vs. 0.44 +/- 0.04 mumol/l, p < 0.0001) and SDMA(0.43 +/- 0.05 vs. 0.34 +/- 0.04 mumol/l, p < 0.0001) and decrease in the Arg/ADMA ratio (118.1 +/- 18.2 vs. 144.3 +/- 22.1, p < 0.0001) in HCM patients. The obstructive HCM subgroup displayed higher values of ADMA, SDMAand sTM compared with the non-obstructive HCM subgroup. HCM patients show specific features of endothelial dysfunction detectable in peripheral blood, involving increased sTM and TFPI, but not vWF, along with increased ADMA levels.

MeSH terms

  • Arginine / analogs & derivatives
  • Arginine / blood
  • Biomarkers / blood
  • Cardiomyopathy, Hypertrophic / blood*
  • Cardiomyopathy, Hypertrophic / diagnosis
  • Cardiomyopathy, Hypertrophic / physiopathology
  • Echocardiography
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Thrombomodulin / blood
  • von Willebrand Factor / analysis

Substances

  • Biomarkers
  • Lipoproteins
  • Thrombomodulin
  • lipoprotein-associated coagulation inhibitor
  • von Willebrand Factor
  • Nitric Oxide
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine