Asimetrični dimetilarginin u bubrežnoj varijanti Fabryjeve bolesti

doctoral thesis

• Title (english): Asymmetric dimethylarginine in renal variant of Fabry disease
• Author: Alen Škrbec
• Mentor: Ksenija Fumić (mentor)
• Committee member: Roberta Petlevski (predsjednik povjerenstva)
• Committee member: Ksenija Fumić (član povjerenstva)
• Committee member: Ingeborg Barišić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2012-07-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Fabryjeva bolest je X-vezana nasljedna metabolička bolest nakupljanja uzrokovana
smanjenom aktivnošću enzima α-galaktozidaze A. Posljednično tome dolazi do nakupljanja
nerazgrađenog supstrata (globotriazilceramida) u endotelnim i glatkim mišićnim stanicama
krvnih žila što dovodi do njihovog oštećenja. Dosadašnji rezultati pokazuju da samo
nakupljeni supstrat nije jedini uzrok kasnijim kliničkim manifestacijama bolesti. Ovo
istraživanje obuhvatilo je određivanje asimetričnog dimetilarginina (ADMA) kao važnog
čimbenika u patologiji promjena endotela krvnih žila u skupini bolesnika s Fabryjevom
bolešću, te koncentracija aminokiselina L-arginina, L-metionina i L-citrulina kao i njihovih
međusobnih omjera s ADMA. Određivanjem koncentracije ADMA u predkliničkoj fazi i za
vrijeme enzimske nadomjesne terapije, željeli smo ispitati da li postoji povezanost genotipa i
fenotipa bolesnika s Fabryjevom bolešću s koncentracijama ADMA u serumu, te procjeniti
moguću klinički primjenu koncentracije ADMA kao novi dijagnostički i prognostički
pokazatelj oštećenja krvnih žila kod bolesnika s Fabryjevom bolesti.
Rezultati pokazuju da ADMA ne može biti pouzdani marker za procjenu stanja bolesnika s
Fabryjevom bolešću. Nadomjestaj L-arginina ili L-citrulina mogao bi biti dodatak ERT kao
prevencija pogoršanja vaskulopatije zbog nedostatka L-arginina i posljedično tome
bioraspoloživosti NO.

Abstract (english)

Fabry disease is X-linked inherited metabolic storage disease caused by reduced activity of
the enzyme α-galactosidase. Consequently that leads to accumulation of substrate
(globotriaosylceramide) in endothelial and smooth muscle cells of blood vessels and to their
damage. Results so far show that only the accumulated substrate is not the only cause of
subsequent clinical manifestations of disease. This research would include determining
asymmetric dimethylarginine (ADMA) as an important factor in the pathology changes of the
endothelium of blood vessels in the patients group with Fabry disease. By determining the
concentration of ADMA in preclinical phase and during enzyme replacement therapy, we will
examine whether there is an association of genotype and phenotype in patients with Fabry
disease with aDMA concentrations in serum and evaluate the possible clinical application of
the concentration of aDMA as a new diagnostic and prognostic marker of vascular damage in
patients with Fabry disease.
This study provides evidence that ADMA could not be reliable marker of vascular damage in
patients with Fabry disease. Supplementation of L-arginine or L-citrulline could be add on
treatment on ERT as prevention of vascular damage due to reduced biosintheses of L-arginine
and availability of NO.

• Keywords: Fabryjeva bolest; α-galaktozidaza A; asimetrični dimetilarginin; L-arginin; Lmetionin; L-cistein; dušikov oksid
• Keywords (english): Fabry disease; α-galactosidase A; asymmetric dimethylarginine; L-arginine; Lmetionine; L-citrulline; nitric oxide
• Language: croatian
• URN:NBN: urn:nbn:hr:163:023179
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-11-16 09:53:28