Rho kinase, a potential target in the treatment of metabolic syndrome

Metabolic syndrome is a health issue which is recognized due to its insulin resistance, central obesity, dyslipidemia, and hypertension. Since the Rho family of GTPases are involved in several cellular mechanisms, it is believed they might be involved in different aspects of metabolic syndrome. We conducted a search of some databases such as PubMed for articles and reviews published between 1997 and 2017, with different keywords including "metabolic syndrome", "rho kinase", "dyslipidemia", "hypertension", "central obesity", "insulin resistance" and the connectors AND or OR. Studies revealed that Rho kinase over-activity leads to cardiovascular diseases, such as hypertension and dyslipidemia, through decreasing NO production. Since NO has beneficial effects on lipid metabolism through activation of hepatic sterol regulatory element-binding protein (SREBP)-2, its inhibition can contribute to higher levels of LDL cholesterol and also results in increased myosin light chain activation with vasoconstriction. Moreover, Rho kinase enhances insulin substrate 1 (IRS-1) phosphorylation, leading to the development of insulin resistance.

In conclusion, the present review demonstrates that upregulated Rho kinase activity involves in the pathogenesis of all aspects of metabolic syndrome. Taken together, these results implicate the therapeutic potential of the Rho-kinase pathway as an important new target in medicine.