Koroner arter hastalığı olgularında LDL oksidasyonu ve risk faktörü olarak paraoksonaz fenotipinin değerlendirilmesi
Küçük Resim Yok
Tarih
2001
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
5. ÖZET Aterosklerotik kardiovasküler hastalık bati toplumlarında en önemli ölüm nedeni ve sağlık sorunudur. Patogenezde diyetsel, çevresel ve genetik faktörler rol oynamakta ve son yıllarda yapılan çalışmalarda "LDL oksidasyonu" önde gelen mekanizmalardan biri olarak vurgulanmaktadır. HDL yapısında bulunan PONİ enzimi, LDL'yi oksidasyona karşı koruyan bir faktör olarak ortaya konmuştur. Genetik polimorfizm gösteren PONİ enziminin farklı fenotiplerinin KAH'a karşı korunmada farklı etkinlikte olduğu belirtilmekte ve sıklıkla, BB fenotipine sahip bireylerde KAH gelişim potansiyelinin yüksek olduğu vurgulanmaktadır. Bu çalışmada, LDL'nin oksidasyona yatkınlığı üzerine farklı PON fenotipleri ve diğer antioksidan enzimlerin etkisi ile PON fenotipinin erken ateroskleroz gelişiminde diğer risk faktörleri ile birlikte bağımsız bir risk faktörü olarak değerlendirilmesi amaçlanmış, koroner anjiografi ile KAH bulunan olgular çalışmaya alınmıştır. Kontrol grubuna (n:24) göre hasta grubunda (n:77) total kolesterol (p: 0.040), trigliserid (p: 0.005), apo B (p: 0.034), CRP (p: 0.027), eritrosit MDA (p: 0.001), bazal LDL-MDA (p: 0.048), indüklenmiş LDL dien (p: 0.042) ve LDL fraksiyonundaki kolesterol (p: 0.012) düzeyi yüksek iken, HDL (p: 0.001), apo Al (p: 0.000) düzeyleri düşüktür. Kontrol grubuna (n:24) göre anjio. N grupta (n:36) eritrosit MDA (p: 0.005) ve LDL fraksiyonundaki kolesterol (p: 0.012) düzeyi yüksektir. Her iki grupta eritrosit SOD ve katalaz aktivitelerinde istatistiksel olarak anlamlı olmayan artış izlenmiştir. Anlamlı stenoz bulunan hasta grubunda CRP düzeyi (p: 0.009) anlamlı stenoz bulunmayan grubun iki katından yüksektir. Kontrol grubuna göre hastalarda, stenoze damar sayısına göre CRP (p: 0.000) ve eritrosit MDA (p: 0.002); total stenoz yüzdesine göre CRP (p:0.000), eritrosit MDA (p: 0.001) ve indüklenmiş LDL dien (p:0.049) düzeylerinde anlamlı artış izlenmiştir. Aile öyküsü bulunanlarda PON aktivitesi bulunmayanlara göre daha düşük bulunmuş ve ailesel yatkınlıkta PON'un önemi ortaya konmuştur. Erkek cinsiyet, yaşlanma, dislipidemi varlığı, hipertansiyon ve sigara risk faktörü olarak ortaya konmuştur. PON fenotipine göre değerlendirmede sadece LDL fosfolipid düzeyi (p: 0.037) farklı fenotipler arasında anlamlı değişiklik göstermiş, ancak PON fenotipi anlamlı bir risk faktörü olarak değerlendirilememiştir. KAH olgularında izlenen değişikliklerin oksidan stres artışını göstermeleri yanısıra eritrosit MDA, bazal ve indüklenmiş LDL dien düzeylerindeki artışın damar stenoz yüzdesi ile paralellik göstermesi bu parametrelerin ateroskleroz için gösterge olarak kullanılabileceğini düşündürmektedir. Çeşitli risk faktörlerine sahip bireylerde erken ateroskleroz göstergesi olarak oksidan stres artışı ile LDL'nin oksidasyona yatkınlığının saptanması yanısıra CRP düzeylerinin izlenmesinin aterosklerotik kardiovasküler hastalığın erken tanısında yararlı olabileceği ve bu çerçevede erken önlem ve tedavi stratejisi geliştirmede zaman kazanılacağı sonucuna varılmıştır. 90
6. SUMMARY Atherosclerotic cardiovascular disease is the main death cause and health problem in western populations. In the pathogenesis; dietical, environmental and genetic factors play an important role and in many recent research "LDL oxidation" is emphasized as priority mechanism. PON1 enzyme, that is present in HDL-cholesterol, has been brought up as a factor that prevents LDL against oxidation. PON1 enzyme which shows genetic polymorphism has different phenotypes and it is determined that these phenotypes have different effects on preventing against CAD and generally, BB phenotype shows a higher CAD risk. In this research, it is aimed that to determine if PON phenotypes and the other antioxidant enzymes have any effect on LDL susceptibility to oxidation and to investigate if PON phenotype, within the other risk factors, is an independent risk factor; so, coronary angiographically verified CAD patients have been taken up to this study. In comparison to control group (n:24), in patient group (n:77), total cholesterol (p: 0.040), trygliceride (p: 0.005), apo B (0.034), CRP (p: 0.027), erythrocyte MDA (p: 0.001), basal LDL MDA (p: 0.048), Cu+2 induced LDL diene (p: 0.042) and cholesterol (p: 0.012) levels in LDL fraction are higher, on the other hand HDL-cholesterol (p: 0.001), apo AI (p: 0.000) levels are lower. In angiographically normal group (n:36), erythrocyte MDA (p: 0.005) and cholesterol (p: 0.012) levels in LDL fraction (p: 0.012) are higher in comparison to control group. In both groups, there is an increase in erytrocyte SOD and catalase activity that is not statistically significant. CRP levels is high at least two-fold in patients which have angioagraphically significant stenosis. In CAD patient groups according to stenosed vessel number, increase in CRP (p: 0.000), erythrocyte MDA (p: 0.002) levels and according to percentage of total vessel stenosis increase in CRP (p: 0.000), erythrocyte MDA (p: 0.001) and Cu+2 induced LDL diene (p: 0.049) levels is significant. PON activity is lower in patients with family history and this shows that PON is important in familial susceptibility to CAD. Male sex, aging, dyslipidemia, hypertension and cigarette smoking are determined as risk factors. Only LDL phospholipid level is (p: 0.037) significantly different between PON phenotype groups, but PON phenotype is not evaluated as a risk factor in CAD. Changes in parameters show us that there is an oxidative stress in CAD patients and increase in eryhtrocyte MDA, basal and induced LDL diene levels suggest that these parameters can be used as an indicator in atherosclerosis. As a conclusion; in high risk people, determining an increase in oxidative stress and LDL susceptibility to oxidation within the following up CRP levels can be wortwhile in early definition of atherosclerotic cardiovascular disease and in that perspective this provide us more time for early definition of CAD and improving new theraupetic strategies. 91
6. SUMMARY Atherosclerotic cardiovascular disease is the main death cause and health problem in western populations. In the pathogenesis; dietical, environmental and genetic factors play an important role and in many recent research "LDL oxidation" is emphasized as priority mechanism. PON1 enzyme, that is present in HDL-cholesterol, has been brought up as a factor that prevents LDL against oxidation. PON1 enzyme which shows genetic polymorphism has different phenotypes and it is determined that these phenotypes have different effects on preventing against CAD and generally, BB phenotype shows a higher CAD risk. In this research, it is aimed that to determine if PON phenotypes and the other antioxidant enzymes have any effect on LDL susceptibility to oxidation and to investigate if PON phenotype, within the other risk factors, is an independent risk factor; so, coronary angiographically verified CAD patients have been taken up to this study. In comparison to control group (n:24), in patient group (n:77), total cholesterol (p: 0.040), trygliceride (p: 0.005), apo B (0.034), CRP (p: 0.027), erythrocyte MDA (p: 0.001), basal LDL MDA (p: 0.048), Cu+2 induced LDL diene (p: 0.042) and cholesterol (p: 0.012) levels in LDL fraction are higher, on the other hand HDL-cholesterol (p: 0.001), apo AI (p: 0.000) levels are lower. In angiographically normal group (n:36), erythrocyte MDA (p: 0.005) and cholesterol (p: 0.012) levels in LDL fraction (p: 0.012) are higher in comparison to control group. In both groups, there is an increase in erytrocyte SOD and catalase activity that is not statistically significant. CRP levels is high at least two-fold in patients which have angioagraphically significant stenosis. In CAD patient groups according to stenosed vessel number, increase in CRP (p: 0.000), erythrocyte MDA (p: 0.002) levels and according to percentage of total vessel stenosis increase in CRP (p: 0.000), erythrocyte MDA (p: 0.001) and Cu+2 induced LDL diene (p: 0.049) levels is significant. PON activity is lower in patients with family history and this shows that PON is important in familial susceptibility to CAD. Male sex, aging, dyslipidemia, hypertension and cigarette smoking are determined as risk factors. Only LDL phospholipid level is (p: 0.037) significantly different between PON phenotype groups, but PON phenotype is not evaluated as a risk factor in CAD. Changes in parameters show us that there is an oxidative stress in CAD patients and increase in eryhtrocyte MDA, basal and induced LDL diene levels suggest that these parameters can be used as an indicator in atherosclerosis. As a conclusion; in high risk people, determining an increase in oxidative stress and LDL susceptibility to oxidation within the following up CRP levels can be wortwhile in early definition of atherosclerotic cardiovascular disease and in that perspective this provide us more time for early definition of CAD and improving new theraupetic strategies. 91
Açıklama
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Anahtar Kelimeler
Biyokimya, Biochemistry
