title: Elevated plasma ADMA contributes to development of endothelial dysfunction in children with acute lymphoblastic leukemia.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Doroszko
authors.affiliation: Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Niedzielska
authors.affiliation: Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Jakubowski
authors.affiliation: Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Julita
authors.initials: J
authors.lastname: Porwolik
authors.affiliation: Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Turek-Jakubowska
authors.affiliation: Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szahidewicz-Krupska
authors.affiliation: Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Mazur
authors.affiliation: Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Chybicka
authors.affiliation: Division of Angiology, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szuba
mesh_terms: D000293:Adolescent; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000187:drug effects*; D045462:Endothelium-Dependent Relaxing Factors / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications*; D012307:Risk Factors
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine