An Update on the Association of Protein Kinases with Cardiovascular Diseases

Author(s): Fakhra Amin, Azaj Ahmed, Anna Feroz, Peerzada Shariq Shaheen Khaki, Mohd Shahnwaz Khan, Shams Tabrez*, Syed Kashif Zaidi, Wesam H. Abdulaal, Anas Shamsi, Wajihullah Khan, Bilqees Bano*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 2 , 2019


Background: Protein kinases are the enzymes involved in phosphorylation of different proteins which leads to functional changes in those proteins. They belong to serine-threonine kinases family and are classified into the AGC (Protein kinase A/ Protein kinase G/ Protein kinase C) families of protein and Rho-associated kinase protein (ROCK). The AGC family of kinases are involved in G-protein stimuli, muscle contraction, platelet biology and lipid signaling. On the other hand, ROCK regulates actin cytoskeleton which is involved in the development of stress fibres. Inflammation is the main signal in all ROCK-mediated disease. It triggers the cascade of a reaction involving various proinflammatory cytokine molecules.

Methods: Two ROCK isoforms are found in mammals and invertebrates. The first isoforms are present mainly in the kidney, lung, spleen, liver, and testis. The second one is mainly distributed in the brain and heart.

Results: ROCK proteins are ubiquitously present in all tissues and are involved in many ailments that include hypertension, stroke, atherosclerosis, pulmonary hypertension, vasospasm, ischemia-reperfusion injury and heart failure. Several ROCK inhibitors have shown positive results in the treatment of various disease including cardiovascular diseases.

Conclusion: ROCK inhibitors, fasudil and Y27632, have been reported for significant efficiency in dropping vascular smooth muscle cell hyper-contraction, vascular inflammatory cell recruitment, cardiac remodelling and endothelial dysfunction which highlight ROCK role in cardiovascular diseases.

Keywords: Cardiovascular disease, Fasudil and Y27632, Protein kinase, ROCK, Rock isomers, Rock inhibitors, Rho-kinase.

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Year: 2019
Page: [174 - 183]
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DOI: 10.2174/1381612825666190312115140
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