Effects of Statins on Circulating Oxidized Low-density Lipoprotein in Patients With Hypercholesterolemia

Inami, Shigenobu; Okamatsu, Kentaro; Takano, Masamichi; Takagi, Gen; Sakai, Shunta; Sano, Junko; Mizuno, Kyoichi

doi:10.1536/jhj.45.969

Cited by 26 publications

(7 citation statements)

References 21 publications

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“…While the reduction in cardiovascular events by statintype drugs is mainly thought to be due to their cholesterol-lowering effects, statins have been shown to exert many other beneficial effects including improvements in vascular endothelial function [23], anti-inflammatory effects, antioxidant effects [24,25], smooth muscle cell proliferation [26], and enhanced stability of atherosclerotic plaques [27]. Abe et al previously reported that fluvastatin, but not simvastatin, increased eNOS mRNA levels by enhancing the transcriptional activities of the eNOS gene and mRNA stability in human umbilical vein endothelial cells [28].…”

Section: Discussionmentioning

confidence: 99%

Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: Efficacy and incidence of cardiac and other events in elderly patients (≥65 years old)

Itakura

Nakaya²,

Kusunoki³

et al. 2011

Journal of Cardiology

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This large-scale, prospective, uncontrolled study confirmed the lipid-lowering efficacy and safety of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients aged ≥ 65 years old. The higher incidence of cardiac and cerebral events in patients aged ≥ 65 years old in the secondary prevention cohort reflects a high-risk clinical profile with multiple classic risk factors warranting multifactorial interventions.

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Section: Discussionmentioning

confidence: 99%

Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: Efficacy and incidence of cardiac and other events in elderly patients (≥65 years old)

Itakura

Nakaya²,

Kusunoki³

et al. 2011

Journal of Cardiology

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“…In fact, several clinical researches revealed such additional benefits of statins to improve patients’ outcome. (8,9) Moreover, several basic researches also showed that statins could reduce hydroxyl radical in vitro , or prevent cholesterol-induced oxidative stress in laboratory animals. (10–12) Fluvastatin is a compound with a fluorophenyl indole ring and an enoic acid, and pravastatin is a compound with a naphthalene frame and an enanthate (Fig.…”

Section: Introductionmentioning

confidence: 99%

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Umeda

Takanari

Ogata

et al. 2019

J. Clin. Biochem. Nutr.

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stricted use, distribution, and reproduction in any medium, provided the original work is properly cited.3 Hydroxy 3 methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (k fv for fluvastatin, and k pv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with k fv and k pv of 4.82 M −1 s −1 and 49.0 M −1 s −1 , respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both k fv and k pv were >10 9 M −1 s −1 . Fluvastatin also eliminated tert butyl peroxyl radical with relative k fv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with k fv and k pv of 68.6 M −1 s −1 and 701 M −1 s −1 , respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.

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“…Furthermore, atherosclerotic plaques from patients with T2D have also been shown to present larger oxLDL areas, commonly associated with inflammation and a rupture-prone plaque phenotype [13]. Statins are known to reduce plasma lipoproteins (LDL and circulating oxLDL), plaque oxLDL and concurrent inflammation [26,27]. Atherosclerotic plaques harvested over the past decade show more stable features [28].…”

Section: Discussionmentioning

confidence: 99%

Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

Singh

Gonçalves

Tengryd

et al. 2020

Cardiovasc Diabetol

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Background Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. Methods Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers. Results Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a). Conclusions This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

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Effects of Statins on Circulating Oxidized Low-density Lipoprotein in Patients With Hypercholesterolemia

Cited by 26 publications

References 21 publications

Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: Efficacy and incidence of cardiac and other events in elderly patients (≥65 years old)

Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: Efficacy and incidence of cardiac and other events in elderly patients (≥65 years old)

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

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