A Differential Review of Statins, Their Distinct Differences, and the Underlying Mechanisms of Vasodilation

Qujeq, Durdi; Pourbagher, Roghayeh; Nosrati Andevari, Ali; Bahri, Faegheh; Pourzaman, Afsaneh; Douseh, Rana

A Differential Review of Statins, Their Distinct Differences, and the Underlying Mechanisms of Vasodilation

Articles in Press

Document Type : Review Article

Authors

Durdi Qujeq

Roghayeh pourbagher

Ali Nosrati Andevari

Faegheh Bahri

Afsaneh pourzaman

Rana douseh

Abstract

Statins exert their effects by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-R) in the mevalonate pathway. The purpose of this study is to investigate statins, their differences, and the associated mechanisms of vasodilation. Seven statins are used in the clinical setting. These statins include atorvastatin, lovastatin, fluvastatin, simvastatin, pravastatin, pitavastatin, and rosuvastatin. Statins differ in several ways, including their origin, membrane permeability, drug interactions, and affinity for HMG-CoA-R. Fungi-derived statins include lovastatin, pravastatin, and simvastatin.
In contrast, atorvastatin, fluvastatin, pitavastatin, and rosuvastatin are produced by chemical synthesis. Furthermore, lipophilic statins, including atorvastatin, lovastatin, simvastatin, fluvastatin, and pitavastatin, but not rosuvastatin and pravastatin, exhibit hydrophilic properties. Hydrophilic statins experience fewer drug interactions than lipophilic statins. Pitavastatin and pravastatin exhibit lower efficacy in reducing cholesterol levels. In contrast, rosuvastatin and atorvastatin lower cholesterol levels more than other statins. Since lipophilic statins readily enter non-hepatic cells, these statins may improve vasodilation more than hydrophilic statins. The action of statins is due to the inhibition of the production or activity of cholesterol, geranyl-geranyl pyrophosphate (GGPP), RhoA/ROCK, phosphatase and tensin homolog (PTEN), and nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and the stimulation of the production or activity of insulin and the PI3K/AKT/eNOS pathway. Considering the more potent inhibitory effect of rosuvastatin on the mevalonate pathway, along with the substantial inhibitory activity of atorvastatin on this pathway and its lipophilic characteristics, these two agents produce a more pronounced vasodilatory effect than other statins.

Keywords

Statin

Vasodilation

Insulin

Cholesterol

GGPP

Subjects