Rho-kinaz enzim sisteminin vasküler kas tonusu üzerine fizyopatolojik etkileri

Amaç: Rho-kinaz enzimleri (ROCKs), küçük bir G proteini olan RhoA’nın ilk efektörlerinden biridir. Son bilgiler Rho/Rho-kinaz yolunun sadece damar düz kas hücrelerinde (DDKH) değil aynı zamanda aktinle hücre iskeletinin organizasyonu, hücre adezyon ve motilitesi, sitokinezis ve gen ekspresyonu gibi çeşitli hücresel fonksiyonlar üzerinde önemli bir fizyolojik rol oynadığını göstermektedir. Ana bulgular: Rho-kinazlar, trombus şekillenmesi, enflamasyon/oksidatif stres ve fibrozisi hızlandırmak suretiyle çeşitli molekülleri artan düzenlemeyle kontrol eder. Rho-kinaz aynı zamanda, DDKH’de hiperkontraksiyon, proliferasyon ve migrasyonun uyarılması ve enflamatuvar hücre motilitesinin artırılmasına aracı olur. Birçok çalışmada, Rho-kinazın vazospazm, arteriyoskleroz, iskemi/reperfüzyon hasarı, hipertansiyon, pulmoner hipertansiyon, inme ve kalp yetmezliği patogenezine ve merkezi sempatik sinir aktivitesinin artırılmasına önemli ölçüde karıştığı gösterilmiştir. Sonuç: Bu derlemede, vasküler kas tonusu üzerine ROCK enzimlerinin fizyolojik rolünü ve ROCK enzim inhibisyonunun ne şekilde kardiovasküler faydalar sağlayabildiği ile ilgili değerlendirmeleri inceledik.

Pathophysiological effects of Rho-Kinase enzyme system on the vascular muscle tone

Objective: Rho kinases (ROCKs) are the first effectors of the small G-protein RhoA. Recent data has demonstrated that Rho/Rho-kinase pathway plays an important physiological role in various cellular functions, not only in vascular smooth muscle cell (VSMC) contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions. Main findings: Rho-kinase upregulates various molecules that accelerate thrombus formation, inflammation/oxidative stress, and fibrosis. At the same time, Rho-kinase mediates VSMC hypercontraction, stimulates VSMC proliferation and migration, and enhances inflammatory cell motility. In the several studies, Rho-kinase has been shown to be substantially involved in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke and heart failure, and to enhance central sympathetic nerve activity. Conclusion: In this review, we reviewed what is known about the physiological role of ROCKs on the vascular muscle tone and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

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