Abstract
Fasudil induced cell proliferatýon in human umbilical ven endothelial cellObjective: This study investigated the effects of a Rho kinase inhibitor on vascular endothelial cells.Material and Methods: Human umbilical venous endothelial cells (HUVECs) were obtained from the AmericanType Culture Collection. Cells were seeded in 96-well gelatin coated microtiter plates at a concentration of1×104 cells/ml in a final volume of 100 µl per well. Three groups were established: a control group andgroups with rho kinase inhibitor (fasudil) added at concentrations of 5 or 6 mM. These baseline cultureswere then observed for 72 hours. Results: A strong linear cell proliferation was seen in the control and therho kinase inhibitor groups. The average concentration was 1.063 for the 5 mMol fasudil group and 1.147for the 6 mM group, and this difference was statistically significant (p=0.044). The number of cells analyzedat 24 to 48 hours showed a significant difference, but the cell numbers between 48 and 72 hours did not differstatistically. Conclusion: Fasudil did not show any cytotoxicity to endothelial cells; on the contrary, itpromoted cell proliferation. The increase in endothelial cell proliferation and vascular stenosis was causedby neointimal hyperplasia, which would be detrimental in diseases such as stent stenosis
Keywords
References
- Hýrata K, Kýkuchý A, Sasaký T, Kuroda S. Involvement of rho p21 in the GTP enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem. 1992;267:8719-8722.
- Fukata Y, Amano M, Kaibuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.Trends Pharmacol Sci. 2001;22(1):32-9.
- Shimokawa H, Rashid M. Development of Rho-kinase inhibitors for cardiovascular medicine. Trends Pharmacol Sci. 2007;28:296-302.
- Mukai Y, Shimokawa H, Mataba T Kandabashi T, Satoh S, Hiroki J, et al. Involvement of Rho-kinase in hypertensive vascular disase:a novel therapeutic target in hypertension. FASEB J. 2001;15(6):1062-4.
- Bao W, Hu E, Tao L, Boyce R, Mirabile R, Thudium DT, et al. Inhibition of Rhokinase protects the heart against ischemia/reperfusion injury. Cardiovasc Res.2004;61(3):548-58.
- Kubat H, Ark M. Ýnsanda Rho-kinazýn rolü. Mersin Üniversitesi Týp Fakültesi Dergisi. 2005; 2 : 153-159
- Riento K, Ridley AJ. Kinases in cell behaviour. Nature 2003; 4 : 446-456.
- Fukata Y, Amano M, Kaibuchi K. RhoRho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. TRENDS in Pharmacological Sciences 2001; 22(1) : 32-39.
- Xiao Sun, Hao Tong, Man Zhang, Xiao-Hang Wang. Rosuvastatin inhibits the smooth muscle cell proliferation by targeting TNFa mediated Rho kinase pathway. Journal of Geriatric Cardiology (2012) 9: 180-184
Abstract
Amaç: Bu çalışma ile rho kinaz inhibitörünün vasküler endotel hücreleri üzerine olan etkileri araştırılmıştır.
Materyal metod: İnsan umbilikal ven endotel hücrelerinin (HUVEC) Amerikan Tip Kültür Koleksiyonundan elde edildi. Hücreler kuyu başına toplam hacmi 100 μl olan jelatin kaplı mikrotitre plaklar içinde mililitrede 104 hücre olacak şekilde 96 kuyuya ekildi. Bazal grup ile 5mMol ve 6mMol konsantrasyonlarda rho kinaz inhibitörü uygulanan iki grup olmak üzere üç grup oluşturuldu. İlaç uygulanmış kültürler ve ilaç uygulanmayan bazal kültürler 72 saat takip edildi.
Bulgular: Kontrol hücreleri ile rho-kinaz inhibitörü (fasudil) verilen hücreler arasında doğrusal artan kuvvetli bir ilişki saptanmıştır. Fasudil konsantrasyonu 5 mMol olanların ortalaması 1.063 iken 6 mMol olanların ortalaması 1.147 olmuştur. Bu ortalamalar arasında istatistiki olarak anlamlı fark bulunmuştur (p:0,044). Zamana göre hücre sayılarında 24 saat ile 48 saat süreleri arasında önemli ölçüde fark oluşmuşken 48 saat ile 72 saat arasında istatistiksel olarak fark oluşmamıştır.
Sonuç: Sonuçlara göre fasudil endotel hücre üzerine sitotoksisite göstermeyip aksine proliferasyonu arttırıyor. Bu da endotel hücre proliferasyonunun artarak neointimal hiperplazi ile vasküler stenoza neden olan stent stenozu gibi hastalıklar için kötü bir durum oluşturmaktadır.
Keywords
References
- Hýrata K, Kýkuchý A, Sasaký T, Kuroda S. Involvement of rho p21 in the GTP enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem. 1992;267:8719-8722.
- Fukata Y, Amano M, Kaibuchi K. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.Trends Pharmacol Sci. 2001;22(1):32-9.
- Shimokawa H, Rashid M. Development of Rho-kinase inhibitors for cardiovascular medicine. Trends Pharmacol Sci. 2007;28:296-302.
- Mukai Y, Shimokawa H, Mataba T Kandabashi T, Satoh S, Hiroki J, et al. Involvement of Rho-kinase in hypertensive vascular disase:a novel therapeutic target in hypertension. FASEB J. 2001;15(6):1062-4.
- Bao W, Hu E, Tao L, Boyce R, Mirabile R, Thudium DT, et al. Inhibition of Rhokinase protects the heart against ischemia/reperfusion injury. Cardiovasc Res.2004;61(3):548-58.
- Kubat H, Ark M. Ýnsanda Rho-kinazýn rolü. Mersin Üniversitesi Týp Fakültesi Dergisi. 2005; 2 : 153-159
- Riento K, Ridley AJ. Kinases in cell behaviour. Nature 2003; 4 : 446-456.
- Fukata Y, Amano M, Kaibuchi K. RhoRho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. TRENDS in Pharmacological Sciences 2001; 22(1) : 32-39.
- Xiao Sun, Hao Tong, Man Zhang, Xiao-Hang Wang. Rosuvastatin inhibits the smooth muscle cell proliferation by targeting TNFa mediated Rho kinase pathway. Journal of Geriatric Cardiology (2012) 9: 180-184
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Dentistry |
| Journal Section | Research Articles |
| Authors | |
| Publication Date | June 30, 2014 |
| Submission Date | November 28, 2012 |
| Published in Issue | Year 2014 Volume: 21 Issue: 2 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.