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ID naloge: 156 Letnik: 2003 Predmet: patofiziologija
VLOGA PROTEOLITICNIH ENCIMOV PRI NASTANKU ANEVRIZME POPLITEALNE ARTERIJE
Avtor: Jurij Štalc, Uroš Tominc
Mentor: doc. dr. Matija Kozak
IZHODIŠCE: Dilatativna ateroskleroza je redka oblika degenerativnega procesa žilne stene, ki se kaže kot anevrizmatsko razširjenje žile. Patogeneza anevrizem ni popolnoma poznana. Za nastanek naj bi bila pomembna proteoliticna razgradnja izvencelicnega matriksa; ob tem omenjajo predvsem sistem matriksnih metaloproteinaz (MMP) in fibrinoliticni sistem.
NAMEN: Namen raziskave je bil oceniti vlogo MMP in fibrinoliticnega sistema pri nastanku anevrizme poplitealne arterije.
HIPOTEZI: 1. Koncentracija MMP-3, -9 in -13 v plazmi je v skupini preiskovancev z anevrizmo poplitealne arterije višja od tiste v skupini preiskovancev s klasicno obliko ateroskleroze. 2. Aktivnost fibrinoliticnega sistema (merjena s testi fibrinoliticnega sistema) je v skupini preiskovancev z anevrizmo poplitealne arterije višja od tiste v skupini preiskovancev s klasicno obliko ateroskleroze.
METODE: V raziskavo smo vkljucili 22 preiskovancev z anevrizmo poplitealne arterije (skupina A: 20 moških, 2 ženski, povprecna starost 62,7 10,3 let) in 17 po starosti, spolu in dejavnikih tveganja za aterosklerozo podobnih preiskovancev s klasicno obliko ateroskleroze (skupina B: 15 moških, 2 ženski, povprecna starost 67,1 10,6 let). Merili smo plazemsko koncentracijo MMP-3, -9, -13, tkivnega aktivatorja plazminogena (t-PA), inhibitorja tkivnega aktivatorja plazminogena 1 (PAI-1), D-dimera, fibrinogena, C-reaktivnega proteina, aktivnost PAI, cas evglobulinske lize (CEL) in protrombinski cas (PC). Razlike med skupinama smo testirali z Mann-Whitneyevim U testom.
REZULTATI: Med skupinama nismo našli statisticno znacilnih razlik v koncentraciji MMP. Ugotovili smo, da so imeli preiskovanci z anevrizmo na antikoagulacijskem zdravljenju (podskupina A+; 11 preiskovancev) statisticno znacilno (p = 0,002) nižje vrednosti koncentracij MMP-3 (mediana 29,6 ng/ml) kot preiskovanci z anevrizmo brez antikoagulacijskega zdravljenja (podskupina A-; 11 pacientov; mediana 132 ng/ml) ali preiskovanci skupine B (mediana 42,8 ng/ml; p = 0,03). Našli smo statisticno znacilno višjo aktivnost PAI (p = 0,04) v skupini A (mediana 9,3 IU/ml) v primerjavi s skupino B (mediana 5,5 IU/ml). Prav tako smo ugotovili statisticno znacilno (p = 0,03) razliko v CEL med podskupino A+ (mediana 380 min) in podskupino A- (mediana 300 min). Podskupina A+ je imela znacilno (p = 0,04) višjo aktivnost PAI (mediana 9,1 IU/ml) kot skupina B (mediana 5,5 IU/ml).
ZAKLJUCKI: Bolniki z anevrizmo poplitealne arterije, ki niso na antikoagulacijskem zdravljenju, imajo, tako kot je v literaturi opisano pri bolnikih z anevrizmo trebušne aorte, višjo plazemsko koncentracijo MMP-3, kar nakazuje pomembnost tega encima v patogenezi poplitealne anevrizme. Bolniki z anevrizmo poplitealne arterije na antikoagulacijskem zdravljenju so imeli znacilno najnižjo koncentracijo MMP-3. Za razlago tega odkritja potrebujemo nadaljnje raziskave. Podaljšan CEL pri bolnikih z anevrizmo na antikoagulacijskem zdravljenju, je posledica ucinkov varfarina. Ugotovili smo vecjo aktivnost PAI v skupini preiskovancev z anevrizmo v primerjavi s skupino preiskovancev s klasicno obliko ateroskleroze, kar je verjetno posledica znotrajžilnega sprošcanja PAI iz trombov. Povezave med fibrinoliticnim sistemom in nastankom poplitealne anevrizme nismo mogli potrditi.
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[Abstract / English version]
VLOGA PROTEOLITICNIH ENCIMOV PRI NASTANKU ANEVRIZME POPLITEALNE ARTERIJE
Author: Jurij Štalc, Uroš Tominc
Mentor: doc. dr. Matija Kozak
BACKGROUND: Dilatative atherosclerosis is a rare form of degenerative process of arteries manifested by arterial aneurysms. The pathogenesis of aneurysm formation is not completely understood, however, involvement of proteolytic degradation of extracellular matrix components (collagen, elastin) due to matrix metalloproteinase (MMP) and fibrinolytic system activity could be important.
AIM: Aim of our study was to assess the significance of matrix metalloproteinase and fibrinolytic system for popliteal artery aneurysm (PAA) formation.
HYPOTHESES: 1. Concentration of MMP-3, -9 and -13 is higher in patients with PAA than in patients with peripheral arterial occlusive disease (PAOD). 2. Fibrinolytic system activity is higher in patients with PAA than in patients with PAOD.
METHODS: The research involved 22 patients with PAA (Group A: 20 males, 2 females, mean age 62.7 10.3) and 17 age-, sex- and atherosclerosis risk factors-matched patients with PAOD (Group B: 15 males, 2 females, mean age 67.1 10.6). Concentrations of MMP-3, -9, -13, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 antigen (PAI-1), D-dimer, fibrinogen, C-reactive protein, PAI activity, euglobulin clot lysis time (ECLT) and prothrombin time (PT/INR) were measured. Mann - Whitney U test was used for statistical comparison.
RESULTS: There was no significant difference in MMP's concentration found between the two groups. However, patients with aneurysm taking warfarin (Subgroup A+; 11 patients) had lower values of MMP-3 concentration (median 29.6 ng/ml) than both patients with aneurysm without warfarin (Subgroup A-; 11 patients; median 132 ng/ml; p = 0.002) and patients belonging to group B (median 42.8 ng/ml; p = 0.03). Moreover, we found significantly higher (p = 0.04) PAI activity in group A (median 9.3 IU/ml) compared to group B (median 5.5 IU/ml). We also found significant difference (p = 0.03) in ECLT between subgroup A+ (median 380 min) and subgroup A- (median 300 min). Subgroup A+ patients had significantly (p = 0.04) higher PAI activity (median 9.1 IU/ml) than group B patients (median 5.5 IU/ml).
CONCLUSIONS: Patients with PAA similarly as in literature described patients with abdominal aorta aneurysm have higher plasma MMP-3 concentration when not treated with warfarin, which might indicate the importance of this enzyme in PAA pathogenesis. However, plasma concentrations of MMP-3 in patients with PAA treated with warfarin are even lower then in patients with PAOD. This finding deserves further study. Besides ECLT, which is prolonged in patients on warfarin because of the therapy, PAI activity is higher in patients with aneurysms than in controls, which is probably due to intravascular thrombi releasing PAI. The research could not confirm a correlation between fibrinolytic system and PAA.
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