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Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Hossein Babaahmadi-Rezaei, Maryam Rezaei, Hossein Ghaderi-Zefrehi, Masoumeh Azizi, Hasti Beheshti-Nasab and Jawahar Lal Mehta*

DOI: 10.2174/1871530322666220606090801

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Reducing Proteoglycan Synthesis and NOX Activity by ROCK Inhibitors: Therapeutic Targets in Atherosclerosis

Page: [1191 - 1200] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Atherosclerosis is a chronic inflammatory disease of the arteries characterized by the accumulation of inflammatory cells in the arterial wall. Hypertension, dyslipidemia, and hyperglycemia are major risk factors of atherosclerosis. Rho-associated protein kinase (ROCK), a serine/threonine kinase, is a downstream effector of the small GTPase RhoA. ROCK is involved in different stages of atherosclerosis. Accumulating evidence has demonstrated that ROCK signaling plays vital roles in various cellular functions, such as contraction, migration, and proliferation of smooth muscle cells. Dysregulation of the ROCK pathway is associated with atherosclerosis and hypertension. Experimental studies have shown that ROCK inhibitors may have favorable effects in ameliorating atherosclerosis. ROCK signaling has a role in proteoglycan synthesis through transactivation of the TGF-β receptor Type I (TβRI) mediated by G-protein-coupled receptor (GPCR) agonists (endothelin-1, angiotensin II and …), and ROCK inhibitors could decrease proteoglycan synthesis and atherosclerotic plaque formation. Based on the hypothesis that targeting ROCK pathway may be effective in ameliorating atherosclerosis, we suggest that ROCK inhibitors may have a potential therapeutic role in inhibition or slowing atherogenesis. However, for this hypothesis more research is needed.

Keywords: Rock, nadph oxidase, atherosclerosis, proteoglycan, transactivation, endothelin-1.

Graphical Abstract

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