The importance of new biomarkers of inflammation and angiogenesis in peripheral arterial disease

Abstract

Periferna arterijska bolest klinička je manifestacija ateroskleroze sa značajnim morbiditetom i mortalitetom. Upala i angiogeneza imaju značajnu ulogu u njenom razvoju, progresiji i komplikacijama. Cilj rada bio je ispitati postoji li povezanost izmeĎu katalitičkih koncentracija i genetskog polimorfizma paraoksonaze (PON1), katalitičkih koncentracija acetil hidrolaze trombocitnog čimbenika aktivacije (PAF-AH), te koncentracija vaskularnog endotelnog čimbenika rasta (VEGF), angiopoietina 2 (Ang-2) i njegovog Tie-2 receptora, kao novih biomarkera u procesu upale i angiogeneze, sa pojavnošću i stupnjem stenotično/okluzivnih promjena perifernih arterija. Snižene katalitičke koncentracije PON1 i polimorfizmi Q192R i -108C>T pon1 gena mogli bi imati ulogu u razvoju periferne arterijske bolesti. Razlike u frekvenciji Q i R alela izmeĎu ispitanika i kontrolne skupine mogu biti jedan od uzroka sniženih katalitičkih koncentracija PON1, što može doprinosti smanjenoj zaštitnoj ulozi HDL-kolesterola i povećanom riziku od prijevremene ateroskleroze kod rizičnih skupina bolesnika. Povećane koncentracije Ang-2 i Tie-2 receptora mogle bi ukazivati na povećano vaskularno remodeliranje kao odgovor na prisutne čimbenike rizika, te bi se mogli smatrati novim biomarkerima angiogeneze koji ukazuju na prisustvo periferne arterijske bolesti. Nepostojanje povezanosti izmeĎu koncentracija istraživanih biokemijskih parametara i angiografskog sustava bodovanja, kao mjere anatomske proširenosti aterosklerotskih promjena perifernih arterija ukazuje na važnost drugih čimbenika u progresiji bolesti.Peripheral artery disease is a clinical manifestation of atherosclerosis with significant morbidity and mortality. Inflammation and angiogenesis play an important role in its development, progression and complications. The aim of this thesis was to investigate the association of the catalytic concentrations and genetic polymorphism of paraoxonase (PON1), the catalytic concentrations of platelet activating factor acetylhydrolase (PAF-AH), the concentrations of vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang-2) and its receptor Tie-2, as novel biomarkers of inflammation and angiogenesis with the appearance and degree of stenotic-occlusive changes in the periphearal arteries. Lower catalytic concentrations of PON1 and polymorphisms Q192R and - 108C>T pon1 gene could play a role in the development of peripheral arterial disease. Differences in the frequency of Q and R alleles between patient and control groups may be one of the causes of the reduced catalytic concentrations of PON1, which may contribute to a reduced protective role of HDL-cholesterol and increased risk of early atherosclerosis in the risk group of patients. An increased concentration of Ang-2 and Tie-2 receptor could indicate increased vascular remodeling in response to the presence of risk factors and could be considered new biomarkers of angiogenesis which indicate the presence of peripheral arterial disease. The absence of significant correlation between the concentrations of the biochemical parameters investigated and the angiographic score as a measure of the anatomic extent of atherosclerotic lesions to the peripheral arteries, suggests that other factors are more important in the progression of the disease