Pleiotropic effects of pitavastatin.
Bottom Line: In addition to the direct effects of statins in reducing concentrations of atherogenic low density lipoprotein cholesterol (LDL-C), several studies have indicated that the beneficial effects of statins may be due to some of their cholesterol-independent, multiple (pleiotropic) effects which may differ between different members of the class.Pitavastatin is a novel synthetic lipophilic statin that has a number of pharmacodynamic and pharmacokinetic properties distinct from those of other statins, which may underlie its potential pleiotropic benefits in reducing cardiovascular risk factors.It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction.
Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.caShow MeSH
Related in: MedlinePlus
Mentions: Lipoprotein oxidation Statins have been shown to reduce the pro-atherogenic effects of oxidized LDL . Specifically, statin-induced activation of the paraoxonase 1 (PON1) gene (mediated by p44/42 mitogen-activated protein kinase signalling) results in inhibition of LDL oxidation [70, 71], and pitavastatin inhibits the uptake of oxidized LDL by macrophages by down-regulating expression of the type B scavenger receptor CD36 . Pitavastatin reduced lectin-like oxidized LDL receptor 1 (LOX-1) in patients with hypercholesterolaemia, but this was not correlated with a reduction in LDL-C . In another study, decreased measures of oxidative stress and lower cardio-ankle vascular index were seen in patients with type 2 diabetes treated with pitavastatin (Figure 6) . These results are clinically important, as oxidative stress is a key pathogenic factor in diabetes. Patients with diabetes often have dysfunctional HDL, and anti-inflammatory, anti-oxidant and cholesterol efflux mechanisms are impaired [75, 76].
Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca