COX-1 Enzimi ve Endotel Disfonksiyon Arasındaki İlişki

Since the discovery of the central role of cyclooxygenase (COX) in the metabolism of arachidonic acid, vascular biologists have been exposed with the duality of this system. Essentially, one substrate (arachidonic acid) converted by one enzyme (COX) yields end products (endoperoxides) that obtain only very briefly before being metabolized to more stable prostanoids by a group of specific synthases that were primarily believed to be tissue specific. For example, thrombocytes include mainly the synthase that produces thromboxane A2 (proaggregatory and vasoconstrictor substance), though endothelial cells contain mainly the enzyme that produces prostacyclin (antiaggregatory and vasodilator substance). The overproduction of thromboxane A2 by thrombocytes induces to thrombosis. Endothelial cells lean against vascular occlusion by producing prostacyclin. This duality of the metabolism of arachidonic acid has ruled over our thinking about atherothrombosis for decades. Based on the review of these studies, we will discuss association between cyclooxygenase enzyme and endothelial dysfunction. GENEL BILGI Siklooksijenazlar, arasidonik asitin prostanoidlere ve diger eikosanoidlere donusumunu katalizleyen enzimlerdir (1). Yapilan bilimsel calismalar ile birlikte siklooksijenazin COX-1 ve COX-2 adli iki izoformunun oldugu ortaya cikmistir . COX-1’in baslangicta pozitif etkili konstitutif izoform oldugu dusunulurken, COX-2’nin agirlikli olarak inflamatuar yanitlarda yer alan negatif etkili bir enzim oldugu dusunulmustur (3). Bununla birlikte, yakin zamanlarda yapilan calismalarla, COX-2 inhibitorlerinin yaygin kullanimindan kaynaklanan kardiyovaskuler hastaliklar icin artmis risk bulunmasi ile COX-2 urunlerinin koruyucu rol oynadiklari ve bu degerlendirilemeyecegi onerilmistir. Benzer sekilde, arasidonik asit metabolizmasinin COX-1 tarafindan baslatilmasinin, vaskuler koruma acisindan aslinda cok da pozitif bir rolunun olmadigi konusunda kanitlar ortaya cikmistir. Bu sonuclar