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
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Mentions: Heart In an animal model of hypertensive heart failure, pitavastatin inhibits load-induced cardiac hypertrophy and fibrosis through inhibition of RhoA-ERK-serum response factor signalling [98, 99]. Pitavastatin reduces remodelling and improves ventricular function in rat hearts through increased eNOS production associated with PI3K signalling and a decrease in oxidative stress . In the absence of eNOS in a mouse model, pitavastatin also reduced cardiac remodelling induced by angiotensin II and renal insufficiency through inhibition of the transforming growth factor-β-Smad signalling pathway by suppression of oxidative stress . Similar results were obtained by Takuwa et al. , who showed that pitavastatin reduces cardiac remodelling, by inhibition of sphingosine kinase 1, and reduces oxidative stress in juvenile mice. Furthermore, in a 12 month randomized, controlled trial in 30 patients with hypercholesterolaemia and preserved left ventricular ejection fraction, treatment with pitavastatin (1 or 2 mg day−1, n= 15) for 1 year significantly reduced carotid arterial stiffness and significantly improved regional left ventricular systolic and diastolic function (P < 0.05) compared with patients given placebo (Figure 7) .
Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca