Publication: Serebrovasküler malformasyonlarda PDGF proteini ve reseptörlerinin ekspresyonu
Abstract
Serebrovasküler malformasyonlar (CVM); arteiovenöz malformasyonlar (AVMler) ve kavernöz malformasyonlar (CMler) santral sinir sisteminin neoplastik olmayan vasküler lezyonlarıdır. Hem AVMler hem de CMler dinamik lezyonlardır ve her iki lezyon tipi anjiogenik olarak aktiftir. Anjiogenez ise vaskülogenezle oluşan damarlardan özgül sinyallerle, kapiller şeklinde yeni damarlar oluşturulması işlemidir. Bu işlemde büyüme faktörleri anahtar rol oynar; PDGF anjiogenik olarak tanımlanan büyüme faktörlerinden biridir. PDGF embriyogenez, yara iyileşmesi, ateroskleroz ve kanser gibi anjiogenezle yakın ilişkili fizyolojik ve patolojik olaylarda rol oynar. Bununla beraber hipoksi ve diğer anjiogenezle ilişkili stimülasyonlar PDGF ekspresyonunu teşvik eder. PDGF ligand ve reseptörleri otokrin ve/ veya parakrin fonksiyonla, anjiogenezi çeşitli yollarla düzenleyebilir. Bu çalışmada AVM ve CM lezyonlarında, anjiogenik özellikdeki PDGF ligand ve reseptörlerinin yoğun şekildeki ekspresyonu gerek immünohistokimyasal yöntemler gerekse de duyarlı moleküler biyolojik bir yöntem olan western blot analizleri ile gösterilmiştir. Elde edilen bulgular, PDGF-AA'nın her iki lezyon tipinde kontrol grubuna göre fazla eksprese edildiğini; lezyonlar birbirleri ile kıyaslandığında ise PDGF-AA ekspresyonun AVMlerde CMlere kıyasla fazla olduğunu göstermiştir. PDGF-AA bağlayan PDGF -reseptörünün AVMlerde, özellikle AVM endotelinde CM endoteline kıyasla fazla eksprese edildiği görülmüştür. PDGF-BB'nin, PDGF-AA'dan daha yoğun olarak her iki lezyon tipinde kontrol grubuna göre fazla eksprese olduğu; PDGF-AA'nın tersine, CM lezyonlarında AVMlere göre fazla eksprese edildiği saptanmıştır. Sadece PDGF-BB ligandına yüksek afinite gösteren PDGF -reseptörünün ise CM endotelinde AVM endoteline kıyasla fazla eksprese edildiği gözlenmiştir. Bu bulgular iki farklı serebrovasküler malformasyonun PDGF sinyal ileti sistemi ile ilişkili olduğunu ancak patogenezlerinde farklı PDGF izoformların etkin olduğunu düşündürmektedir. The Expression of PDGF Ligands and Their Receptors in Cerebrovascular Malformations
Cerebrovascular malformations (CVM); arteriovenous malformations (AVMs) and cavernous malformations (CMs) are defined as non-neoplastic lesions consist of abnormal blood vessels of central nervous system. Both AVMs and CMs are dynamic lesions and they are both angiogenically active. Angiogenesis is a process which new kapilleries are developed from existing vessels. In this process growth factors play key role; PDGF is one of these angiogenic growth factors. PDGF has important roles in processes which have close relations with physiological and pathological angiogenesis; like embryonal development, wound healing, atherosclerosis and cancer. Hipoxia and angiogenesis related stimuli can induce PDGF expression. PDGF ligands and receptors regulate angiogenesis in an autocrine and/ or paracrine fashion. In this work we investigate the role of PDGF ligands and receptors in AVM and CM pathogenesis. We also examine the relation between the factors play role in CVM pathogenesis and PDGF pathway. Both immunohistochemical methods and western blott analysis showed that PDGF ligands and receptors are expressed in these lesions strongly. In conclusion, PDGF-AA is expressed strongly in both lesions campared with control group. When we compare two lesions; AVMs express PDGF-AA stronger than CMs in total. PDGF receptor- which has more affinity to PDGF-A, expression is specifically more in AVM endothelium than CM endothelium. PDGF-BB is expressed stronger than PDGF-AA in both lesion type when compared to control group and expression is stronger in CMs compared to AVMs in total. PDGF receptor- which binds only PDGF-B ligand, is specifically expressed more in CM endothelium than AVM endothelium. These datas suggest that two different subgroups of cerebrovascular malformations have a relation with PDGF signal transduction pathway and different isoforms of PDGF ligands and receptors are more effective in these lesions' pathogenesis.
Cerebrovascular malformations (CVM); arteriovenous malformations (AVMs) and cavernous malformations (CMs) are defined as non-neoplastic lesions consist of abnormal blood vessels of central nervous system. Both AVMs and CMs are dynamic lesions and they are both angiogenically active. Angiogenesis is a process which new kapilleries are developed from existing vessels. In this process growth factors play key role; PDGF is one of these angiogenic growth factors. PDGF has important roles in processes which have close relations with physiological and pathological angiogenesis; like embryonal development, wound healing, atherosclerosis and cancer. Hipoxia and angiogenesis related stimuli can induce PDGF expression. PDGF ligands and receptors regulate angiogenesis in an autocrine and/ or paracrine fashion. In this work we investigate the role of PDGF ligands and receptors in AVM and CM pathogenesis. We also examine the relation between the factors play role in CVM pathogenesis and PDGF pathway. Both immunohistochemical methods and western blott analysis showed that PDGF ligands and receptors are expressed in these lesions strongly. In conclusion, PDGF-AA is expressed strongly in both lesions campared with control group. When we compare two lesions; AVMs express PDGF-AA stronger than CMs in total. PDGF receptor- which has more affinity to PDGF-A, expression is specifically more in AVM endothelium than CM endothelium. PDGF-BB is expressed stronger than PDGF-AA in both lesion type when compared to control group and expression is stronger in CMs compared to AVMs in total. PDGF receptor- which binds only PDGF-B ligand, is specifically expressed more in CM endothelium than AVM endothelium. These datas suggest that two different subgroups of cerebrovascular malformations have a relation with PDGF signal transduction pathway and different isoforms of PDGF ligands and receptors are more effective in these lesions' pathogenesis.