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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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Changes in (A) urinary 8-hydroxy-2′-deoxyguanosine (a marker of oxidative stress), (B) malondialdehyde-LDL (a form of oxidized LDL) and (C) cardio-ankle vascular index in 45 patients with type 2 diabetes mellitus treated with pitavastatin 2 mg day−1 for 12 months (mean ± SD). Urinary 8-hydroxy-2′-deoxyguanosine and malondialdehyde-LDL were measured using enzyme-linked immunosorbent assays. The results for the former were adjusted for serum creatinine concentrations. The cardio-ankle vascular index reflects the stiffness of the aorta and femoral and tibial arteries, independent of blood pressure, and was measured using blood pressure cuffs attached to the biceps and ankles with patients in a supine position. *P < 0.05; **P < 0.01 vs. before treatment, paired t-test. Adapted from Miyashita et al. [74]. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAVI, cardio-ankle vascular index; MDA-LDL, malondialdehyde-low-density lipoprotein
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fig06: Changes in (A) urinary 8-hydroxy-2′-deoxyguanosine (a marker of oxidative stress), (B) malondialdehyde-LDL (a form of oxidized LDL) and (C) cardio-ankle vascular index in 45 patients with type 2 diabetes mellitus treated with pitavastatin 2 mg day−1 for 12 months (mean ± SD). Urinary 8-hydroxy-2′-deoxyguanosine and malondialdehyde-LDL were measured using enzyme-linked immunosorbent assays. The results for the former were adjusted for serum creatinine concentrations. The cardio-ankle vascular index reflects the stiffness of the aorta and femoral and tibial arteries, independent of blood pressure, and was measured using blood pressure cuffs attached to the biceps and ankles with patients in a supine position. *P < 0.05; **P < 0.01 vs. before treatment, paired t-test. Adapted from Miyashita et al. [74]. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAVI, cardio-ankle vascular index; MDA-LDL, malondialdehyde-low-density lipoprotein

Mentions: Lipoprotein oxidation Statins have been shown to reduce the pro-atherogenic effects of oxidized LDL [2]. 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 [72]. 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 [73]. 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) [74]. 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].


Pleiotropic effects of pitavastatin.

Davignon J - Br J Clin Pharmacol (2012)

Changes in (A) urinary 8-hydroxy-2′-deoxyguanosine (a marker of oxidative stress), (B) malondialdehyde-LDL (a form of oxidized LDL) and (C) cardio-ankle vascular index in 45 patients with type 2 diabetes mellitus treated with pitavastatin 2 mg day−1 for 12 months (mean ± SD). Urinary 8-hydroxy-2′-deoxyguanosine and malondialdehyde-LDL were measured using enzyme-linked immunosorbent assays. The results for the former were adjusted for serum creatinine concentrations. The cardio-ankle vascular index reflects the stiffness of the aorta and femoral and tibial arteries, independent of blood pressure, and was measured using blood pressure cuffs attached to the biceps and ankles with patients in a supine position. *P < 0.05; **P < 0.01 vs. before treatment, paired t-test. Adapted from Miyashita et al. [74]. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAVI, cardio-ankle vascular index; MDA-LDL, malondialdehyde-low-density lipoprotein
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig06: Changes in (A) urinary 8-hydroxy-2′-deoxyguanosine (a marker of oxidative stress), (B) malondialdehyde-LDL (a form of oxidized LDL) and (C) cardio-ankle vascular index in 45 patients with type 2 diabetes mellitus treated with pitavastatin 2 mg day−1 for 12 months (mean ± SD). Urinary 8-hydroxy-2′-deoxyguanosine and malondialdehyde-LDL were measured using enzyme-linked immunosorbent assays. The results for the former were adjusted for serum creatinine concentrations. The cardio-ankle vascular index reflects the stiffness of the aorta and femoral and tibial arteries, independent of blood pressure, and was measured using blood pressure cuffs attached to the biceps and ankles with patients in a supine position. *P < 0.05; **P < 0.01 vs. before treatment, paired t-test. Adapted from Miyashita et al. [74]. 8-OHdG, 8-hydroxy-2′-deoxyguanosine; CAVI, cardio-ankle vascular index; MDA-LDL, malondialdehyde-low-density lipoprotein
Mentions: Lipoprotein oxidation Statins have been shown to reduce the pro-atherogenic effects of oxidized LDL [2]. 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 [72]. 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 [73]. 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) [74]. 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].

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