Endotel hasarı sonrası gelişen vasküler düz kas proliferasyonunda telomer devamlılığında araştırılması
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Dosyalar
Tarih
2007
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Düz kas hücre proliferasyon ve/veya migrasyonuna bağlı olarak gelişen intimal
hiperplazinin ateroskleroz patojenezi ile balon anjiyoplasti sonrası oluşan restenozdan
sorumlu olduğu bilinmektedir. Ökaryotik hücrelerde, kromozomların uçlarında bulunan
telomerler kromozomal bütünlüğünü korumak üzere etkinlik gösterirler. Söz konusu
telomerler kromozomal replikasyon sürecinin sürdürülmesinde ve yine hücresel
yaşlanma sürecinin zamanlanmasında anahtar bir rol oynarlar. Telomer devamlılığı
telomeraz enziminin aktivitesi ile sürdürülür. Yüksek oranda proliferasyon gösteren
hücrelerde telomeraz aktivitesinin arttığı gösterilmiştir. Bunun yanı sıra, damar düz kas
hücrelerinde telomeraz aktivitesinin arttığı ve telomeraz inhibisyonunun ise damar düz
kas hücre büyümesini engellediği de gösterilmiştir.
Bu açıdan bakıldığında, ateroskleroz ve balon anjiyoplasti sonrası gelişen restenozun
patojenezindeki telomeraz aktivitesi ve telomer devamlılığının rolü tam olarak
saptanamamıştır. Bu projede vasküler düz kas hücre proliferayonunda telomeraz
aktivitesinin rolü ile düz kas hücre proliferasyonu ve telomer devamlılığı arasındaki
ilişkinin araştırılması amaçlanmıştır.
Bu amaçla tavşan ilyak arterine balon anjiyoplasti uygulanmış ve daha sonra hasar
gören ve görmeyen ilyak arterler izole edilerek telomeraz aktivitesi ve telomer
devamlılığı araştırılmıştır. Bunun yanı sıra ilyak arter segmentlerinde intimal
hiperplaziyi saptamak üzere morfometrik ve immünohistokimyasal analizler
gerçekleştirilmiştir.
Çalışmamızın sonuçları ilyak artere balon anjiyoplasti uygulamasının, hasar görmüş
arterlerde damar düz kas hücrelerinin intimal tabakaya göç etmesinden kaynaklanan bir
intimal hiperplaziye neden olduğunu göstermiştir. Ayrıca, hasar gören ilyak arter
segmentlerinde telomeraz aktivitesi saptanmamıştır. Çalışmamızın sonuçları, bunların
yanı sıra, hasar görmüş ilyak arter damar segmentlerinde telomerik restriksiyonel
fragmanların kısaldığına işaret etmektedir.
It has been reported that intimal hyperplasia, due to smooth muscle cell proliferation and migration, is responsible for the pathogenesis of atherosclerosis and restenosis occuring after balloon angioplasty. In eucaryotic cells, the telomer is found at the end of linear chromosomes and acts to preserve chromosomal integrity. Telomers play a key role in mediating the processes of chromosomal replication and in regulating the timing of cellular aging processes. Telomeres are maintained by the activity of the enzyme telomerase. Telomerase activity is found to be increased in highly proliferative cells. Besides, it has been shown that telomerase activity is increased in vascular smooth muscle cells whereas inhibition of telomerase diminished growth of vascular smooth muscle cells. In this context, the role of telomer maintenance and telomerase activity in the pathogenesis of atherosclerosis and restenosis occuring after balloon angioplasty has not been fully determined. The proposed project aims to investigate the role of telomerase in the proliferation of vascular smooth muscle cells and the relationship between smooth mucle cell proliferation and telomer maintenance. For this purpose, balloon angioplasty was performed in the iliac artery of the rabbits and thereafter telomerase activity and telomer maintenance were investigated in the isolated injured and non-injured arteries. In addition, morphometric and immunohistochemical analyses were conducted in order to determine intimal hyperplasia in arterial segments. Our results demonstrated that balloon angioplasty in iliac arteries resulted in intimal hyperplasia due to the migration of smooth muscle cells to the intimal layer. In addition telomerase activity has not been detected in injured arteries. Our results also showed that small size telomeric restrictional fragments were evident in injured arteries.
It has been reported that intimal hyperplasia, due to smooth muscle cell proliferation and migration, is responsible for the pathogenesis of atherosclerosis and restenosis occuring after balloon angioplasty. In eucaryotic cells, the telomer is found at the end of linear chromosomes and acts to preserve chromosomal integrity. Telomers play a key role in mediating the processes of chromosomal replication and in regulating the timing of cellular aging processes. Telomeres are maintained by the activity of the enzyme telomerase. Telomerase activity is found to be increased in highly proliferative cells. Besides, it has been shown that telomerase activity is increased in vascular smooth muscle cells whereas inhibition of telomerase diminished growth of vascular smooth muscle cells. In this context, the role of telomer maintenance and telomerase activity in the pathogenesis of atherosclerosis and restenosis occuring after balloon angioplasty has not been fully determined. The proposed project aims to investigate the role of telomerase in the proliferation of vascular smooth muscle cells and the relationship between smooth mucle cell proliferation and telomer maintenance. For this purpose, balloon angioplasty was performed in the iliac artery of the rabbits and thereafter telomerase activity and telomer maintenance were investigated in the isolated injured and non-injured arteries. In addition, morphometric and immunohistochemical analyses were conducted in order to determine intimal hyperplasia in arterial segments. Our results demonstrated that balloon angioplasty in iliac arteries resulted in intimal hyperplasia due to the migration of smooth muscle cells to the intimal layer. In addition telomerase activity has not been detected in injured arteries. Our results also showed that small size telomeric restrictional fragments were evident in injured arteries.
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