Necat YILMAZ, Esin EREN, Cemile ÖZ, Seçkin Özgür TEKELİ

Bilirubin metabolizması ve aterosklerozdaki rolü

Hemoglobin bir dizi aterosklerotik hastalığın patofizyolojisinde suçsuz bir seyirci değildir. Hemoglobinden veya diğer hem proteinlerinden salınan hem hücre içi stresin yanında hem stresi de dahil olmak üzere çeşitli patofizyolojik sonuçları tetikler. Hemin anahtar fonksiyonları olması ve sıkı bir şekilde kontrol edilmesine rağmen, çeşitli patofizyolojik koşullarda ortaya çıkabilen yüksek serbest heme seviyeleri, pro-oksidan, proenflamatuar ve sitotoksik etkiler nedeniyle tehlikeli olabilir. Hem oksijenazlar, hemi bir substrat olarak kullanan ve tüm insan hücreleri tarafından gerekli bir antioksidan adaptif yanıt olarak işlev gören ısı şoku protein enzimleridir. Hem oksijenazların en önemli fonksiyonu eritrosit döngüsüne bağlı dokularda biriken hemin temizlenmesidir. Potansiyel toksik serbest hem hem oksijenazları tarafından karbon monoksit, demir ve biliverdine dönüştürülür, bunlardan üçüncüsü bilirubine indirgenir. Literatürde hem degradasyon yolunun ateroskleroz gelişimine karşı koruyucu bir rol oynadığı gösterilmiştir. Çünkü artan kanıtlar oksidatif stresin aterosklerozda rol oynadığını düşündürmektedir. Bu derleme bilurubinin aterosklerozdaki rollerini belgelemekte ve koroner arter hastalığı gibi aterosklerotik hastalıklarda potansiyel bir terapötik hedef olarak klinik öneme odaklanmaktadır.

Bilirubin metabolism and its role in atherosclerosis

Hemoglobin is not an guiltless bystander of the pathophysiology in a number of atherosclerotic diseases. Heme,which is released from hemoglobin or other heme proteins, triggers various pathophysiological consequence,including heme stress as well as intracellular stress. Although heme serves key functions and is tightlycontrolled, high levels of free heme, which may occur in various pathophysiological conditions, are mayhazardous via pro-oxidant, pro-inflammatory, and cytotoxic effects.Heme oxygenases are heat shock protein enzymes that use heme as a substrate and function as an essentialantioxidant adaptive response by all human cells. A major function of heme oxygenases is clearance of hemethat accumulate in tissues due to erythrocyte turnover. The potentially toxic free heme is converted by hemeoxygenases into carbon monoxide, iron, and biliverdin, the third of which is reduced to bilirubin. In literature theheme degradation pathway has been demonstrated to play a protective role against the development ofatherosclerosis. Because growing evidence suggests that oxidative stress is involved in atherosclerosis.This review documents the roles of bilurubin in atherosclerosis and focuses on the clinical significance as apotential therapeutic target in atherosclerotic diseases, such as coronary artery disease.

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