Nalan AKYÜREK, Ümit ÖZYURDA, Günseli ÇABUKÇUOĞLU, Çağın ZAİM, Serkan DURDU, Ahmet Rüçhan AKAR, Ömer AKYÜREK

Kalıcı fibrilasyon sürecindeki insan sağ atriyal miyositlerinde apoptotik protein ekspresyonları

Amaç: Bu çalışmada atriyal fibrilasyon (AF)�n patogenezinde apoptozisin rolü araştırıldı.Çalışma planı: Mitral kapak cerrahisine alınan ardışık 30 hasta çalışmaya dahil edildi. Kalıcı AF�i olan 11 hasta (6 erkek, 5 kadın; ort. yaş 57.7±13.1 yıl; dağılım 36-76 yıl) AF grubunu, normal sinüs ritmindeki 19 hasta (11 erkek, 8 kadın; ort. yaş; 64.1±8.4 yıl; dağılım 48-77 yıl) ise kontrol grubunu oluşturdu. Ekokardiyografi ile ölçülen ortalama sol atriyum çapı, AF grubundaki hastalarda 54.8±3.4 mm; kontrollerde ise 40.7±4.1 mm olarak belirlendi (p=0.001). Tüm hastalarda sağ atriyal doku örnekleri ekstrakorporeal dolaşıma girilmeden önce alındı. Atriyal dokularda apoptozisin belirlenmesi için TUNEL yöntemi ile in situ DNA fragmantasyon analizi yapıldı. Bunlara ek olarak anti-apoptotik Bcl-2 ve pro-apoptotik Bax proteinleri immünohistokimyasal yöntemle araştırıldı.Bulgular: Bax ve Bcl-2 protein ifadeleri AF grubu ve kontrollerde benzer oranlarda bulundu (sırasıyla ortalama, %16.2�e karşın %15.1, p=0.73; %14.6�a karşın %16.1, p=0.64). Ancak, kontrollerle kıyaslandığında atriyal miyosit apoptozis, AF grubunda anlamlı derecede (sırasıyla, ortalama apoptotik indeks %21.9� karşın %11.8; p=0.002) yüksek idi. Atriyal dokusu kalıcı AF�en etkilenmiş olan hastaların atriyal miyosit çekirdekleri belirgin şekilde TUNEL pozitifliği gösterirken, kontrol grubundaki hastaların büyük çoğunluğu TUNEL negatif veya düşük yoğunlukta TUNEL pozitifliği paterni sergiledi.Sonuç: Bu pilot çalışmayla, apoptozisin terminal belirteci olan DNA fragmantasyonu ile AF arasında pozitif ilişki olduğu gösterildi. Bu sonuçlar, kalıcı AF patogenezinde atriyal miyosit apoptozisinin rolü olduğunu düşündürmektedir. Anti-apoptotik hedefli stratejilerin atriyal yeniden biçimlenme ve fibrozisin önlenmesi açısından klinik bir önemi olabilir.

Apoptotic protein expressions in human right atrial myocytes with permanent fibrillation

Background: The aim of this study was to investigate the role of apoptosis in the pathogenesis of atrial fibrillation (AF).Methods: Thirty consecutive patients submitted for mitral valve surgery were investigated. Eleven patients with permanent AF (6 males, 5 females; mean age 57.7±13.1 years; range 36 to 76 years) were considered as the AF group whereas 19 patients who were in sinus rhythm (11 males, 8 females; mean age 64.1±8.4 years; range 48 to 77 years) were selected as control subjects. Mean left atrial diameter determined by echocardiography was 54.8±3.4 mm in the AF group compared to 40.7±4.1 mm in controls (p=0.001). The right atrial appendage tissue samples were excised before extracorporeal circulation in all patients. We assessed the onset of in situ DNA fragmentation by using the TUNEL assay. Furthermore, we examined the expression pattern of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins using immunohistochemistry.Results: Bax and Bcl-2 expression were similar between the AF group and control subjects (16.2% versus 15.1%, p=0.73; 14.6% versus 16.1%, p=0.64, respectively). However, when compared with controls, atrial myocyte apoptosis was significantly higher within the AF group (mean apoptotic index, 21.9% versus 11.8% respectively, p=0.002). Atrial tissue from permanent AF-affected individuals had atrial myocyte nuclei that were positive for TUNEL whereas control subjects had either TUNEL negative or low-grade TUNEL positivity.Conclusion: This pilot study demonstrated a positive correlation between AF and DNA fragmentation, a terminal determinant of apoptosis. The results suggest a potential link between the pathogenesis of permanent AF and atrial myocyte apoptosis. Targeted anti-apoptotic strategies may have a clinical value by preventing atrial remodeling and fibrosis.

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