Turkiye Klinikleri Journal of Internal Medicine

.: REVIEW
Endoplazmik Retikulum Stresi ve Hipertansiyon
Endoplasmic Reticulum Stress and Hypertension
Sevtap HANa, Mecit Orhan ULUDAĞa, Emine DEMİREL YILMAZb
aFarmakoloji ABD, Gazi Üniversitesi Eczacılık Fakültesi,
bTıbbi Farmakoloji ABD, Ankara Üniversitesi Tıp Fakültesi, Ankara, TÜRKİYE
Turkiye Klinikleri J Intern Med. 2019;4(3):147-53
doi: 10.5336/intermed.2019-65618
Article Language: TR
Full Text
ÖZET
Hipertansiyon, oldukca sık rastlanan ve toplum sağlığını onemli derecede tehdit eden bir hastalıktır. Bu konuda fazlaca araştırma yapılmış olmasına rağmen, pek cok etkenin yer aldığı hipertansiyon patogenezi henuz tam olarak anlaşılamamıştır. Gunumuzde, hipertansiyonda klasik semptomatik tedaviler uygulanmaya devam etmektedir. Bu nedenle, hipertansiyon patogenezinin aydınlatılması, secici tedavi stratejilerinin geliştirilmesi acısından oldukca onemlidir. Endoplazmik retikulum (ER), hucresel stresi erken donemde algılayarak yanıt oluşturan bir organeldir. ER, protein sentezi icin kalite kontrol merkezi olarak tanımlanmıştır. Katlanmamış veya yanlış katlanmış proteinler ER'de tutularak degarde edilirken, sadece doğru bir şekilde katlanmış proteinler ER'den cıkmaktadır. ER'nin lumenine katlanmamış ya da yanlış katlanmış proteinlerin birikmesiyle ortaya cıkan durum, endoplazmik retikulum stresi (ERS) olarak adlandırılmaktadır. ER'nin işlev kapasitesini aşan genel protein sentezinin artışı, kalsiyum homeostazı değişimleri, oksidatif stres ve hipoksi gibi bazı patolojiler ERS'ye yol acmaktadır. ERS'nin erken evrelerinde bircok koruyucu ve adaptif yanıt devreye girmektedir. Uzun sureli ERS sonucunda ise hucrede işlev bozuklukları oluşmaktadır. Son zamanlarda, ERS'nin onlenmesi ya da ortadan kaldırılması; hipertansiyon, kalp yetersizliği gibi kardiyovaskuler hastalıkların tedavisinde potansiyel bir hedef olarak one surulmuştur. İlk olarak beyindeki ERS'nin kronik hipertansiyonda anahtar rol oynadığını gosterilmiştir. Daha sonraki yıllarda, hayvanlarda farklı deneysel hipertansiyon modellerinde yapılan calışmalar, ERS'nin hipertansiyon etiyopatogenezindeki rolunu ortaya koymuştur. Bu calışma, kardiyovaskuler sistemde ERS'nin hipertansiyon oluşumu ve gelişimine katkılarını ve ERS'ye yonelik tedavi stratejilerini kapsamaktadır.

Anahtar Kelimeler: Hipertansiyon; endoplazmik retikulum stresi
ABSTRACT
Hypertension is the most common cardiovascular disease, which is a major threat to public health. Although there has been much research on this subject, the pathogenesis of hypertension, which involves many factors, has not been fully understood. While classic symptomatic treatments continue to be applied, clarification of the pathogenesis of hypertension is important for the development of selective treatment strategies. Endoplasmic reticulum (ER), which responds to cellular stress in an early period, is defined as a quality control center for protein synthesis. Only properly folded proteins are transported from ER while unfolded or misfolded proteins are retained and degraded. Endoplasmic reticulum stress (ERS) is the accumulation of unfolded or misfolded protein in the lumen of the endoplasmic reticulum (ER). It is caused by pathological conditions that overwhelm the functional capacity of the ER, such as an increase in overall protein synthesis, changes in calcium homeostasis, redox imbalance, and hypoxia. Recently, the inhibition or reduction of ERS has been recognized as a potential target for the treatment of cardiovascular diseases, such as hypertension and heart failure. It has been firstly shown that ERS in the brain plays a key role in chronic hypertension. Furthermore, various experimental models have been used to investigate the role of ERS in the pathogenesis of hypertension. This review highlights the role of ERS in the etiopathogenesis of hypertension and the treatment strategies that target ERS.

Keywords: Hypertension; endoplasmic reticulum stress
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