Title:Reducing Proteoglycan Synthesis and NOX Activity by ROCK Inhibitors:
Therapeutic Targets in Atherosclerosis
Volume: 22
Issue: 12
Author(s): Hossein Babaahmadi-Rezaei, Maryam Rezaei, Hossein Ghaderi-Zefrehi, Masoumeh Azizi, Hasti Beheshti-Nasab and Jawahar Lal Mehta*
Affiliation:
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical
Sciences, Little Rock, Arkansas 72205, United States
Keywords:
Rock, nadph oxidase, atherosclerosis, proteoglycan, transactivation, endothelin-1.
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.