An update on the association of protein kinases with cardiovascular diseases.

BACKGROUND: Protein kinases are the enzymes involved in phosphorylation of different proteins and leads to functional changes in those proteins. They are classified into the AGC (Protein kinase A/ Protein kinase G/ Protein kinase C) families of protein and Rho-associated kinase protein (ROCK) and belong to serine-threonine kinases family. 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.

METHODS: Two ROCK isoforms are found in mammals and invertebrates. The first isoforms are found mainly in the kidney lung, spleen, liver, and testis. The second one is mainly distributed in the brain and heart. Inflammation is the main signal in all ROCK mediated disease. It trigger the cascade of reaction involving various pro-inflammatory cytokines molecule.

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 their role in cardiovascular diseases.