Rho Kinaz ve Kardiyovasküler Hastalıklar

Öz

Abstract Rho Kinase and Cardiovascular Diseases Arterial diseases such as arteriosclerosis and hypertension are characterized by proliferation and hypertrophy of smooth muscle cells. The common feature of these diseases is endothelial dysfunction, which regulates the growth and tone of vascular smooth muscle cells. Inflammatory mediators like tumor necrosis factor alfa, interleukin-1β cause accumulation and adhesion of monocytes to the vessel wall by up-regulation of monocyte chemotactic peptide-1 and adhesion molecules such as vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, as well as migration, proliferation of vascular smooth muscle cells, and vessel obstruction. Rho kinase, sub-effector of small G protein Rho has two isoforms named as ROKα/ROCK II and ROKβ/ROCK I. ROCK mediates various cellular functions such as smooth muscle contraction, actin cytoskeleton formation, cell adhesion and motility, proliferation, cytokinesis, and gene expression that play a role in pathogenesis of cardiovascular diseases. Preclinical and clinical studies with selective ROCK inhibitors, fasudil and Y-27632, have shown that ROCK has an important role in the pathogenesis of cardiovascular diseases such as coronary vasospasm, hypertension, pulmonary hypertension, angina, myocardial infarction, stroke and heart failure. Also, beneficial effects of prolonged inhibition of ROCK in cardiovascular diseases have been demonstrated. The role of ROCK inhibitors in the treatment of various cardiovascular diseases was evaluated in this review.

Anahtar Kelimeler

• ROCK I, ROCK II, Rho kinase inhibitors, cardiovascular diseases

Rho Kinaz ve Kardiyovasküler Hastalıklar

Öz

Türkçe Özet: Rho Kinase and Cardiovascular Diseases Ateroskleroz, hipertansiyon gibi arteriyel hastalıklar, düz kas hücrelerinin çoğalması ve hipertrofisi ile belirgindir. Bu hastalıkların ortak özelliği, damar düz kas hücre gerimini ve büyümesini düzenleyen endotel tabakasındaki işlev bozukluğudur. Tümör nekroze edici faktör-α, interlökin-1β gibi yangıya neden olan mediyatörler monosit kemotaktik peptit-1, damar hücre adezyon molekülü-1 ve hücrelerarası adezyon molekülü-1 gibi adezyon moleküllerinin up-regüle olarak monositlerin damar duvarında birikmesine ve adezyonuna-yapışmasına ayrıca damar düz kas hücre göçüne, çoğalmasına ve damar tıkanmasına yol açmaktadır. Küçük G proteini Rho'nun alt efektörü Rho kinaz'ın ROKα/ROCK II ve ROKβ/ROCK I olmak üzere iki izoformu bulunmaktadır. ROCK, düz kas kasılması, aktin hücre iskeleti oluşumu, hücre yapışması ve hareketliliği, çoğalması, sitokinez ve genetik bilginin genden proteine aktarılması gibi kardiyovasküler hastalıkların patojenezinde rol oynayan çeşitli hücre işlevlerine aracılık etmektedir. Fasudil ve Y-27632 gibi seçici ROCK inhibitörleri ile yapılan klinik öncesi ve klinik çalışmalarda ROCK'nin kardiyovasküler sistem ile ilgili olarak ortaya çıkan koroner vazospazm, hipertansiyon, miyokart infarktüsü, inme ve kalp yetmezliği gibi çeşitli hastalıkların patojenezinde önemli rol oynadığı gösterilmiştir. Ayrıca, ROCK'nin uzun süre baskılanmasının kardiyovasküler hastalıkların tedavisinde yararlı etkileri gösterilmiştir. Bu derlemede, ROCK inhibitörlerinin çeşitli kardiyovasküler hastalıkların tedavisindeki rolü değerlendirilmiştir.

Anahtar Kelimeler

• ROCK I, ROCK II, Rho kinaz inhibitörleri, kardiyovasküler hastalıklar

Kaynakça

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