Elevated plasma ADMA contributes to development of endothelial dysfunction in children with acute lymphoblastic leukemia

Postepy Hig Med Dosw (Online). 2016 Jun 1;70(0):562-71. doi: 10.5604/17322693.1203720.

Abstract

Background: Childhood acute lymphoblastic leukemia (ALL) survivors are at higher cardiovascular risk than the general population, which may result from anthracycline-related endothelial dysfunction (ED). However, a few studies indirectly show that ED may appear in ALL children before treatment begins. Hence, in this study we intended to verify the hypothesis that ED is part of the ALL phenotype.

Patients/methods: Twenty-eight ALL children and 14 healthy age-matched control children were recruited. The study group was examined at baseline, then at the 33rd and 78th day of treatment. At each step of the protocol endothelial vasodilative function was assessed by a laser Doppler flowmeter, which was followed by blood collecting for subsequent analyses.

Results: Compared to controls, the study group at baseline was characterized by significantly lower endothelial vasodilative responsiveness, accompanied by elevated asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations, which were correlated with lactate dehydrogenase (LDH) and aspartate transaminase (AST). Initial ALL treatment restored endothelial function, which followed changes in ADMA and LDH concentrations.

Discussion: This is the first demonstration that functionally assessed ED is present in ALL children at the diagnosis and results from elevated ADMA and parallel inflammatory ED.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / etiology*
  • Child
  • Child, Preschool
  • Endothelial Cells / drug effects*
  • Endothelium-Dependent Relaxing Factors / therapeutic use*
  • Enzyme Inhibitors / blood*
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Risk Factors

Substances

  • Endothelium-Dependent Relaxing Factors
  • Enzyme Inhibitors
  • N,N-dimethylarginine
  • Arginine