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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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Isoprene synthesis, separate from cholesterol synthesis, modulates cellular function by activating GTPases and G-proteins, such as Ras, Rac1 and RhoA, via addition of an isoprene chain (farnesol or geranylgeraniol). Statin-induced decreases in HMG-CoA reductase activity reduce downstream protein prenylation and have the potential to improve vascular function through multiple pathways. GTP, guanosine triphosphate; PAI-1, plasminogen activator inhibitor-1; Ras, rat sarcoma subfamily; Rac1, Ras-related C3 botulinum toxin substrate 1; RhoA, Ras homologue gene family, A
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fig02: Isoprene synthesis, separate from cholesterol synthesis, modulates cellular function by activating GTPases and G-proteins, such as Ras, Rac1 and RhoA, via addition of an isoprene chain (farnesol or geranylgeraniol). Statin-induced decreases in HMG-CoA reductase activity reduce downstream protein prenylation and have the potential to improve vascular function through multiple pathways. GTP, guanosine triphosphate; PAI-1, plasminogen activator inhibitor-1; Ras, rat sarcoma subfamily; Rac1, Ras-related C3 botulinum toxin substrate 1; RhoA, Ras homologue gene family, A

Mentions: The pleiotropic effects of statins may act at multiple points in the complex cascade of events leading to atherosclerosis. Decreases in mortality and morbidity seen in the major trials of statins may therefore reflect multi-faceted actions on the atherosclerotic process. Figure 2 illustrates the cellular mechanisms by which statin-induced reductions in serum mevalonate, the direct reaction product of HMG-CoA reductase and HMG-CoA, may influence vascular function. Reductions in protein prenylation (the addition of an isoprene chain such as farnesol, 15 carbon atoms, or geranylgeraniol, 20 carbon atoms) have diverse, multiple effects on atherosclerotic processes including vasodilation, oxidative stress, inflammation and thrombosis. The evidence for the effects of statins, particularly pitavastatin, on reducing the pathophysiological processes that lead to atherosclerosis is described below.


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Isoprene synthesis, separate from cholesterol synthesis, modulates cellular function by activating GTPases and G-proteins, such as Ras, Rac1 and RhoA, via addition of an isoprene chain (farnesol or geranylgeraniol). Statin-induced decreases in HMG-CoA reductase activity reduce downstream protein prenylation and have the potential to improve vascular function through multiple pathways. GTP, guanosine triphosphate; PAI-1, plasminogen activator inhibitor-1; Ras, rat sarcoma subfamily; Rac1, Ras-related C3 botulinum toxin substrate 1; RhoA, Ras homologue gene family, A
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Isoprene synthesis, separate from cholesterol synthesis, modulates cellular function by activating GTPases and G-proteins, such as Ras, Rac1 and RhoA, via addition of an isoprene chain (farnesol or geranylgeraniol). Statin-induced decreases in HMG-CoA reductase activity reduce downstream protein prenylation and have the potential to improve vascular function through multiple pathways. GTP, guanosine triphosphate; PAI-1, plasminogen activator inhibitor-1; Ras, rat sarcoma subfamily; Rac1, Ras-related C3 botulinum toxin substrate 1; RhoA, Ras homologue gene family, A
Mentions: The pleiotropic effects of statins may act at multiple points in the complex cascade of events leading to atherosclerosis. Decreases in mortality and morbidity seen in the major trials of statins may therefore reflect multi-faceted actions on the atherosclerotic process. Figure 2 illustrates the cellular mechanisms by which statin-induced reductions in serum mevalonate, the direct reaction product of HMG-CoA reductase and HMG-CoA, may influence vascular function. Reductions in protein prenylation (the addition of an isoprene chain such as farnesol, 15 carbon atoms, or geranylgeraniol, 20 carbon atoms) have diverse, multiple effects on atherosclerotic processes including vasodilation, oxidative stress, inflammation and thrombosis. The evidence for the effects of statins, particularly pitavastatin, on reducing the pathophysiological processes that lead to atherosclerosis is described below.

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