Targeting Rho and Rho-kinase in thromboinflammation

Atherosclerosis is a multi-factorial inflammatory disease defined by the interaction of excessive inflammation and lipid buildup. In recent years, substantial evidence has emerged that statins, through their so-called \"pleiotropic effects,\" might reduce vascular inflammation and slow the progression of atherosclerosis. The capacity to block isoprenoid production is primarily responsible for these cholesterol-independent effects. Inhibition of geranylgeranylpyrophosphate synthesis, in particular, causes Rho and its downstream target, Rho-kinase, to be inhibited (ROCK). As a result, one of statin therapy\'s positive benefits might be attributable to its inhibitory effects on ROCK. ROCK has a role in smooth muscle contraction, cell migration, and proliferation, among other biological processes. While increased ROCK activity is linked to endothelial dysfunction, cerebral ischemia, coronary vasospasms, and metabolic syndrome, statins or selective ROCK inhibitors block ROCK, resulting in enhanced endothelial nitric oxide synthase (eNOS) and decreased metabolic syndrome.