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Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

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Treatment with pitavastatin (2 mg day−1) for 4 weeks increased serum urocortin concentrations, measured using an enzyme-linked immunosorbent assay, in 15 healthy male volunteers. *P < 0.01 vs. before pitavastatin treatment. Reproduced with permission from Honjo et al. [68]
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fig05: Treatment with pitavastatin (2 mg day−1) for 4 weeks increased serum urocortin concentrations, measured using an enzyme-linked immunosorbent assay, in 15 healthy male volunteers. *P < 0.01 vs. before pitavastatin treatment. Reproduced with permission from Honjo et al. [68]

Mentions: Pitavastatin has been shown to reduce oxidative stress in hypercholesterolaemic rabbits [65] and to reduce elevated levels of reactive oxygen species and NADPH oxidase activity in genetically obese rats [66]. In addition, a reduction in angiotensin II-induced atrial remodelling can be attributed to decreased atrial production of O2−• in pitavastatin-treated mice [67]. Pitavastatin also increases the plasma concentrations of urocortin, which is produced in endothelial cells and inhibits the formation of reactive oxygen species (Figure 5) [68]. This pleiotropic effect, which has not been reported for other statins, is of interest because urocortin is a potent vasodilator that may lower blood pressure and increase K+ATP channel gene expression. Urocortin may also have inotropic and cardio-protective effects in ischaemia–reperfusion injury and beneficial cardiovascular effects in heart failure in humans [69].


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Treatment with pitavastatin (2 mg day−1) for 4 weeks increased serum urocortin concentrations, measured using an enzyme-linked immunosorbent assay, in 15 healthy male volunteers. *P < 0.01 vs. before pitavastatin treatment. Reproduced with permission from Honjo et al. [68]
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376429&req=5

fig05: Treatment with pitavastatin (2 mg day−1) for 4 weeks increased serum urocortin concentrations, measured using an enzyme-linked immunosorbent assay, in 15 healthy male volunteers. *P < 0.01 vs. before pitavastatin treatment. Reproduced with permission from Honjo et al. [68]
Mentions: Pitavastatin has been shown to reduce oxidative stress in hypercholesterolaemic rabbits [65] and to reduce elevated levels of reactive oxygen species and NADPH oxidase activity in genetically obese rats [66]. In addition, a reduction in angiotensin II-induced atrial remodelling can be attributed to decreased atrial production of O2−• in pitavastatin-treated mice [67]. Pitavastatin also increases the plasma concentrations of urocortin, which is produced in endothelial cells and inhibits the formation of reactive oxygen species (Figure 5) [68]. This pleiotropic effect, which has not been reported for other statins, is of interest because urocortin is a potent vasodilator that may lower blood pressure and increase K+ATP channel gene expression. Urocortin may also have inotropic and cardio-protective effects in ischaemia–reperfusion injury and beneficial cardiovascular effects in heart failure in humans [69].

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.

View Article: PubMed Central - PubMed

Affiliation: Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal (IRCM) and University of Montréal, QC, Canada. Jean.Davignon@ircm.qc.ca

Show MeSH
Related in: MedlinePlus