İskemik Kalp Hastalarında Trombosit Fonksiyonu Üzerine Mitokondri mt4977 Delesyonunun Etkileri

Öz

Amaç: Bireylerin farklı dokularındaki mitokondriyal DNA’larında (mtDNA) nokta mutasyonları, duplikasyonlar ve delesyonlar meydana geldiği bilinmektedir. Gözlenen delesyonlar içerisinde 8470-8482 ile 13447-13459 nükleotid pozisyonlarında yer alan ve 4977 baz çiftinin kaybına yol açan mtDNA 4977 mutasyonu en sık olarak görülmtedir. mtDNA 4977 delesyonu solunum zinciri komplekslerinin alt ünitlerini kodlayan 8 genin kaybolmasına yol açar. Buna bağlı olarak delesyonun oksidatif fonksiyonu engellemesi ve ATP üretim düzeyini azaltması beklenebilir. Mitokondriyal ATP üretiminin trombosit fonksiyonları üzerinde önemli bir rolü olduğu bilinmektedir. Ancak bununla ilişkili olarak literatürde herhangi bir bilgi göze çarpmamaktadır. İskemik kalp hastalığında (İKH) trombosit aktivasyonunun hastalık fizyopatolojisinde önemli bir rol oynadığı gösterildiğinden, bu çalışmamızda trombosit fonksiyonu ile mtDNA 4977 delesyonu arasındaki ilişkiyi ve iskemik kalp hastalığı gelişimindeki olası etkilerini araştırmayı amaçladık . Gereç ve Yöntem: Trombosit fonksiyonları, sekresyon ve agregasyon açısından değerlendirilmek üzere lumiagregometre cihazı yardımı ile ADP uyaranı verilerek çalışıldı. ATP ölçümü biyolüminesans test kiti ile yapıldı. mt4977 delesyonu, modifiye edilmiş eşzamanlı kantitatif polimeraz zincir reaksiyonu (RT-PCR) yöntemi ile belirlendi. Bulgular: Hastaların trombositlerinde mtDNA 4977 delesyon sıklığı ve mtDNA kopya sayısı sağlıklı kontrol grubuna göre daha yüksekti (p <0.05). Ancak her iki grup arasında trombosit ATP içeriği ile bunların eğim (Ω) ve % amplitüd değerlerinde anlamlı farklılık gözlenmedi (p> 0.05). Sonuç: Sağlıklı kontrol denekleriyle karşılaştırıldığında, İKH hastalarında artmış delesyonun trombosit disfonksiyonu üzerinde anlamlı bir etkiye sahip olmadığı görülmüştür.

Anahtar Kelimeler

• mtDNA4977 delesyonu
• iskemik kalp hastalığı
• trombosit
• ATP

The Effects of Mitochondrial Mt4977 Deletion on Platelet Function in Ischemic Heart Disease Patients

Öz

Objective: It is known that point mutations, duplications and deletions occur in mitochondrial DNAs (mtDNA) of different tissues of individuals. Among the deletions observed, mt4977 mutation, which is located at nucleotide positions 8470-8482 and 13447-13459 and causes the loss of 4977 base pairs, is the most common. mtDNA 4977 deletion leads to the loss of 8 genes encoding subunits of respiratory chain complexes. Consequently, the deletion could be expected to inhibit the oxidative function and reduce ATP production level. It is known that mitochondrial ATP production has an important role on platelet functions. However, there is no information about this in the literature. Since platelet activation in ischemic heart disease (IHD) has been shown to play an important role in the pathophysiology of the disease, we wanted to examine the relationship between platelet function and mtDNA 4977 deletion in ischemic heart disease. Material and Method: Platelet functions were studied by giving ADP stimulus with the help of lumiaggregometer device to evaluate in terms of secretion and aggregation. ATP measurement was performed with the bioluminescence assay kit. mtDNA 4977 deletion was determined by the modified simultaneous quantitative polymerase chain reaction method. Results: The frequency of mtDNA 4977 deletion and mtDNA copy number were higher in platelets of the patients compared with the healthy control group (p<0.05). However, no significant differences in platelet ATP content, and in their slope (Ω) and % amplitude values were observed between both groups (p>0.05). Conclusion: It was observed that increased deletion in patients with IHD did not have a significant effect on platelet dysfunction compared with healthy control subjects.

Anahtar Kelimeler

• mtDNA4977 deletion
• ischemic heart disease
• platelet
• ATP

Kaynakça

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