Hiperlipidemi ve hiperglisemi kaynaklı oksidatif stresin endotel disfonksiyonu üzerine etkileri
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Dosyalar
Tarih
2021
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Hatay Mustafa Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Endotelyum, kan damarlarının ve lenfatik damarların iç yüzeyini kaplayan, tek tabaka endotel hücrelerinden oluşur. Endotel doku, bir fiziksel bariyer gibi görünmekle birlikte, aynı zamanda bazı vazoaktif bileşiklerin oluşturulup salındığı yerdir. Endotel disfonksiyonu, Nitrik oksit (NO) ekspresyonu ve biyoyararlınımının azalması ve genellikle asetilkolinin normal endotel bağımlı vazodilatasyon tepkilerinin kaybı ile gelişir. Serum NO miktarı azalırken endotelin-1 (ET-1) seviyeleri artar ve bu dengesizlik sonucu vazodilatasyon bozulur, adezyon molekülleri artar ve endotel fonksiyonları bozulur. Bu karmaşık süreci başlatan endotel disfonksiyonun altında yatan en yaygın neden oksidatif strestir. Uzun süre yüksek glukoz konsantrasyonuna maruz kalma ile serbest yağ asidi birikimi metabolik substrat mevcudiyetinde değişikliklere neden olabilir ve bu değişiklikler oksidatif strese neden olur. Çalışmamızda yüksek glukoz içeren besiyeri ile görece düşük glukoz içeren besiyerinde çoğaltılan HUVEC, farklı konsantrasyonlarda palmitik aside (PA) maruz bırakılarak (24 saat) yüksek glukoz ve serbest yağ asidinin HUVEC hücrelerinde endotel difonksiyon oluşumuna etkisini araştırdık. Bunun için endotel disfonksiyonunda kilit rol oynayan ET-1(endotelin-1), eNOS(endotelyal nitrik oksit sentaz), VCAM-1(vasküler hücresel adhezyon molekülü-1), PAI-1(plazminojen aktivatör inhibitör-1) ve proinflamatuar sitokinler TNF-a(tümör nekrozis faktörü-alfa) ve IL-6(interlökin-6) gen ekspresyon düzeylerini reverse(ters) transkriptaz real time PCR yöntemi kullanarak belirledik. Sonuç olarak, çalışmamızda farklı konsantrasyonda glukoz ve palmitik asit maruziyetine uğrayan HUVEC hücrelerinde ET-1, PAI-1 ve TNF‐a gen ekspresyon düzeylerindeki artış bu hücrelerde yüksek konsantrasyon glukoz ve serbest yağ asitlerinin birlikteliğinde endotel disfonksiyonu üzerinde daha etkili olduğu ortaya konmuştur.
The endothelium consists of a single layer of endothelial cells lining the inner surface of blood vessels and lymphatic vessels. While endothelial tissue appears to be a physical barrier, it is also the place where some vasoactive compounds are created and released. Decreased nitric oxide expression and bioavailability and loss of normal endothelial-dependent vasodilatation responses of acetylcholine usually occur. While the amount of serum nitric oxide (NO) decreases, the levels of endothelin-1 (ET-1) increase and as a result of this imbalance, vasodilation deteriorates, adhesion molecules increase and endothelial functions are impaired. Oxidative stress is the most common underlying cause of endothelial dysfunction that initiates this complex process. With prolonged exposure to high glucose concentration, free fatty acid accumulation can cause changes in the availability of metabolic substrate, and these changes cause oxidative stress. In our study, we investigated the effect of high glucose and free fatty acid on the formation of endothelial diffusion in HUVECs by exposing them to 0.25, 0.5 and 1 mM PA (24 hours), which were grown in a medium containing high glucose and a medium containing relatively low glucose. For this, we determined the gene expression levels of ET-1, eNOS, VCAM, PAI-1 and proinflammatory cytokines TNF-a and IL-6, which play a key role in endothelial dysfunction, using Real Time PCR method. In conclusion, in our study, it was revealed that the increase in the expression levels of ET-1, PAI-1 and TNF ‐ a genes in HUVEC cells exposed to high concentrations of glucose and palmitic acid is more effective on endothelial dysfunction when high concentration glucose and free fatty acids are present in these cells.
The endothelium consists of a single layer of endothelial cells lining the inner surface of blood vessels and lymphatic vessels. While endothelial tissue appears to be a physical barrier, it is also the place where some vasoactive compounds are created and released. Decreased nitric oxide expression and bioavailability and loss of normal endothelial-dependent vasodilatation responses of acetylcholine usually occur. While the amount of serum nitric oxide (NO) decreases, the levels of endothelin-1 (ET-1) increase and as a result of this imbalance, vasodilation deteriorates, adhesion molecules increase and endothelial functions are impaired. Oxidative stress is the most common underlying cause of endothelial dysfunction that initiates this complex process. With prolonged exposure to high glucose concentration, free fatty acid accumulation can cause changes in the availability of metabolic substrate, and these changes cause oxidative stress. In our study, we investigated the effect of high glucose and free fatty acid on the formation of endothelial diffusion in HUVECs by exposing them to 0.25, 0.5 and 1 mM PA (24 hours), which were grown in a medium containing high glucose and a medium containing relatively low glucose. For this, we determined the gene expression levels of ET-1, eNOS, VCAM, PAI-1 and proinflammatory cytokines TNF-a and IL-6, which play a key role in endothelial dysfunction, using Real Time PCR method. In conclusion, in our study, it was revealed that the increase in the expression levels of ET-1, PAI-1 and TNF ‐ a genes in HUVEC cells exposed to high concentrations of glucose and palmitic acid is more effective on endothelial dysfunction when high concentration glucose and free fatty acids are present in these cells.
Açıklama
Anahtar Kelimeler
Genetik, Genetics ; Tıbbi Biyoloji
