Genetic Basis in Stroke Treatment: Targets of Potent Inhibitors

Stroke is a complex disease resulting from a combination of vascular, environmental and genetic factors. Different therapeutic strategies for the treatment of stroke include antiplatelet therapy, anticoagulants, and lipid- lowering drugs. These drugs act via diverse mechanisms of action and target specific enzymes. The enzymes increase the levels of ubiquitous secondary molecules that can cause changes in vascular tone, increase platelet aggregation, cholesterol levels, and other cellular events. Several inhibitors have been developed to curb these enzymes and thus prevent a recurrent stroke. The most potent inhibitors given in the stroke treatment include inhibitors of angiotensin-converting enzyme (ACE) (perindopril, ramipril), phosphodiesterases (PDEs) (rolipram), GpIIb/IIIa and 3-hydroxy-3-methyl-glutryl- coenzyme A reductase (HMG-CoA reductase) (pravastatin). ACE inhibitors block the ACE enzyme, thereby preventing the conversion of inactive decapeptide angiotensin I to the active octapeptide and potent vasoconstrictor angiotensin II. Angiotensin II plays a pivotal role in the development of hypertension, atherosclerosis and thrombotic events like stroke. Other inhibitors like phosphodiesterase inhibitors (PDEIs) prevent the inactivation of intracellular mediators of signal transduction such as cAMP and cGMP. These mediators are critical to the regulation of platelet functions. PDEIs are used as antiplatelet agents in clinical settings. Statins are given as lipidlowering drugs to reduce the risk of stroke by decreasing blood cholesterol levels through inhibition of liver enzyme β-hydroxymethyl glutaryl coenzyme A reductase enzyme. The current chapter will focus on the recent developments in stroke treatment, especially focussing on potent inhibitors such as PDE, ACE, and HMG.

Keywords: Angiotensin-converting enzyme, Compounds, HMG-CoA reductase, Inhibitors, Phosphodiesterase, Platelet activation, Platelet aggregation, SNP, Stroke, Thromboembolism.