An Update on the Association of Protein Kinases with Cardiovascular Diseases

Author:

Amin Fakhra1,Ahmed Azaj2,Feroz Anna2,Khaki Peerzada Shariq Shaheen2,Khan Mohd Shahnwaz3,Tabrez Shams4,Zaidi Syed Kashif4,Abdulaal Wesam H.5,Shamsi Anas2,Khan Wajihullah1,Bano Bilqees2

Affiliation:

1. Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh (U.P.), India

2. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh (U.P.), India

3. Protein Research Chair, Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia

4. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

5. Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

Abstract

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.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmacology

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