Statins: 3Hydroxy3-methylglutaryl-CoA (HMG-CoA) Reductase Inhibitors Demonstrate AntiAtherosclerotic Character due to Their Antioxidant Capacity (original) (raw)
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Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities
Atherosclerosis, 2004
Low-density lipoprotein (LDL) cholesterol is an established risk factor for coronary heart disease (CHD). In the presence of oxidative stress LDL particles can become oxidized to form a lipoprotein species that is particularly atherogenic. Indeed, oxidized LDL (oxLDL) is pro-inflammatory, it can cause endothelial dysfunction and it readily accumulates within the arterial wall. Several factors may influence the susceptibility of LDL to oxidation, including its size and composition, and the presence of endogenous antioxidant compounds, such as ␣-tocopherol. Individuals with type 2 diabetes or the metabolic syndrome have high levels of oxidative stress and consequently are at an increased risk for cardiovascular events. Reducing oxidative stress has been proposed as a potential approach to prevent CHD and antioxidant vitamins have been employed with encouraging results in experimental models of atherosclerosis. However, clinical trials have not demonstrated consistent beneficial effects of antioxidants on cardiovascular outcomes. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the first-line choice for lowering total and LDL cholesterol levels and they have been proven to reduce the risk of CHD. Recent data suggest that these compounds, in addition to their lipid-lowering ability, can also reduce the production of reactive oxygen species and increase the resistance of LDL to oxidation. It may be that the ability of statins to limit the oxidation of LDL contributes to their effectiveness at preventing atherosclerotic disease. (R.S. Rosenson). may also be at increased risk of developing CHD. Indeed, although levels of LDL may not be elevated, its atherogenic potential may be increased by oxidative modification.
A comparative study of the in vitro antioxidant activity of statins
International Journal of Cardiology, 2003
Background: Treatment of hypercholesterolemia with statins is remarkably effective in cardiovascular prevention. This has led to the hypothesis that these drugs may act on the atherosclerotic plaque by mechanism(s) independent of the reduction of serum cholesterol levels. The aim of this study was to assess the total antioxidant activity of the most prescribed statins: fluvastatin, atorvastatin, pravastatin and simvastatin. Methods: We measured the in vitro antioxidant activity of statins as their ability to antagonize the oxidation of a-keto-g-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Uric acid and Trolox were used as the reference antioxidants. Results: The scavenging capacity towards hydroxyl radicals was highest for simvastatin (33756112 U / mg), a value 270.2% higher (P,0.0001) compared to uric acid (reference antioxidant vs. hydroxyl radicals, 1249671 U / mg). Among the tested statins, fluvastatin exhibited the highest anti-peroxyl radical antioxidant capacity (87556187 U / mg) which appeared 50% lower (P,0.0001) compared to Trolox (reference antioxidant vs. peroxyl radicals, 17 4606379 U / mg). Conclusions: All the statins tested have intrinsic antioxidant activity with both anti-hydroxyl and peroxyl radical activity. Simvastatin was the most effective as an anti-hydroxyl radical antioxidant and fluvastatin as an anti-peroxyl radical antioxidant.
Current Topics in Medicinal Chemistry, 2014
Cardiovascular diseases, which are the leading cause of mortality in the Western World, are closely associated with atherosclerosis development. Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by endothelial dysfunction, inflammation and oxidative stress. Oxidative stress is an alteration of the balance between pro-oxidant and antioxidant mechanisms which promotes vascular complications and represents a valid therapeutic target to prevent or treat cardiovascular diseases. Statins are enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that have been included in the therapeutic regimen of cardiovascular diseases due to their lipid-lowering activity. Experimental and clinical data demonstrated that the antiatherogenic effects of these drugs are also related to other pleiotropic activities, particularly to their anti-inflammatory, antithrombotic and antioxidant effects. This review summarizes experimental and clinical studies demonstrating the impact of statins on atherosclerotic disease with a focus on the antioxidant activity of atorvastatin. Atorvastatin is a synthetic statin characterized by a high efficacy, in part due to its longer half-life compared to other molecules of the same group. It also exerts high antioxidant effects, independent from its hypolipidemic activity, beneficial for the prevention and therapy of atherosclerosis.
Antioxidant effects of simvastatin in primary and secondary prevention of coronary heart disease
European Journal of Clinical Pharmacology, 2006
Objective: The aim of the present study was to determine the effect of simvastatin on the levels of oxidized low-density lipoprotein (ox-LDL) and free radicals in hypercholesterolemic subjects undergoing primary and secondary prevention of coronary heart disease (CHD). Methods: Fifteen subjects with hypercholesterolemia and no obvious CHD and 29 subjects with hypercholesterolemia and stable angina received 40 mg of simvastatin daily for 12 weeks. Serum total cholesterol, HDL-cholesterol and triglyceride concentrations were determined by automated enzymatic assays whereas LDL-cholesterol was calculated using the Friedwald formula. The ox-LDL levels were determined by a commercially available ELISA kit. Free radicals were assessed by the Free Radical Analytical System (FRAS). Results: Both in primary and secondary prevention, subjects had borderline levels of free radicals but in neither group there was a significant reduction of free radicals after simvastatin treatment. In subjects undergoing primary prevention of CHD, ox-LDL levels were reduced by 31.1±5.0% (P<0.001) whereas in secondary prevention were reduced by 6.5±5.2% (P<0.02) after simvastatin treatment. The reduction of ox-LDL levels did not correlate with the reduction of total cholesterol levels in either group studied. In both groups, ox-LDL levels were not associated with free radical levels either before or after simvastatin treatment. Conclusion: This study demonstrates that simvastatin can significantly reduce circulating ox-LDL levels both in subjects undergoing primary and secondary prevention of CHD. These results could partly explain the slowing down of the progression of atherosclerosis caused by HMG-CoA reductase inhibitors.
Antioxidant effects of statins in the management of cardiometabolic disorders
Journal of atherosclerosis and thrombosis, 2014
Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems. Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidatio...
Lipids, 2011
Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterollowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P \ 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.
Statins and Oxidative Stress During Atherogenesis
European Journal of Cardiovascular Prevention & Rehabilitation, 2003
Oxidised low-density lipoprotein (LDL) is believed to be the most atherogenic form of LDL. However, while a number of experimental data support this concept, the protective role of antioxidants that may prevent LDL oxidation in atherosclerosis is only partially confirmed by studies in man. Observational and epidemiological data as well as randomised trials failed to provide clear-cut indications, because of mixed results on the protective role of antioxidants against cardiovascular diseases. In spite of the lack of a general consensus, recent data reinforce the concept that a regular intake of antioxidants present in food blocks the progression of atherosclerosis and that the reduced ability of LDL to oxidise may represent a good marker to follow the action of antioxidants. Among their properties statins also possess antioxidant activities and the aim of this paper is to review the scientific evidence for such an effect and its possible clinical relevance.
Effects of statins on oxidative stress
Biological Trace Element Research, 2004
Free oxygen radicals and insufficient antioxidant enzymes have been implicated in the pathogenesis of hypercholesterolemia (HC). Trace elements function as cofactors in antioxidant enzymes. Antioxidant system and trace elements were investigated in many different studies including HC, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in hypercholesterolemic patients given fluvastatin therapy.