Endothelial Protection, AT
            <sub>1</sub>
            Blockade and Cholesterol-Dependent Oxidative Stress

Morawietz, Henning; Erbs, Sandra; Holtz, J.; Schubert, Andreas; Krekler, Michael; Göettsch, Winfried; Kuß, Oliver; Adams, Volker; Lenk, Karsten; Mohr, Friedrich W.; Schuler, Gerhard; Hambrecht, Rainer

doi:10.1161/circulationaha.105.001313

Cited by 67 publications

(48 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, 49 patients undergoing scheduled CABG were randomized to placebo, pravastatin (40 mg/day), irbesartan (150 mg/day), or both for 4 weeks (69). Statin treatment, as well as combination therapy, significantly increases eNOS and suppresses gp91 phox expression in the left IMA, suggesting a synergistic effect on endothelial function, independently of LDL-lowering effects (69). We have recently demonstrated that short-term treatment with atorvastatin rapidly suppresses O 2 -generation and NADPH oxidase activity in SVGs from patients undergoing CABG, independently of LDL-lowering effects (Fig.…”

Section: Fig 4 Effects Of Statins On Enos In Ecsmentioning

confidence: 84%

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Margaritis

Channon

Antoniades

2014

Antioxidants & Redox Signaling

117

View full text Add to dashboard Cite

Significance: Endothelial dysfunction and the imbalance between nitric oxide (NO) and reactive oxygen species production in the vascular endothelium are important early steps in atherogenesis, a major socioeconomic health problem. Statins have well-established roles in primary and secondary prevention of cardiovascular disease (CVD), due to both their lipid-lowering capacity and their pleiotropic properties. It is therefore important to understand the mechanisms by which statins can modify endothelial function and affect atherogenesis. Recent Advances: In the last decade, the concept of statin pleiotropy has been reinforced by a large number of cell culture, animal, and translational studies. Statins have been shown to suppress the activity of pro-oxidant enzymes (such as NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium. At the same time, they enhance endothelial NO synthase expression and activity while they also improve its enzymatic coupling. This leads to increased NO bioavailability and improved endothelial function. Critical Issues: Despite significant recent advances, the exact mechanisms of statin pleitropy are still only partially understood. The vast majority of the published literature relies on animal studies, while the actual mechanistic studies in humans are limited. Future Directions: The success of statins as endothelium redox-modifying agents with a direct impact on clinical outcome highlights the importance of the endothelium as a therapeutic target in CVD. Better understanding of the mechanisms that underlie endothelial dysfunction could lead to the design of novel therapeutic strategies that target the vascular endothelium for the prevention and treatment of CVD. Antioxid. Redox Signal. 20, 1198Signal. 20, -1215

show abstract

Section: Fig 4 Effects Of Statins On Enos In Ecsmentioning

confidence: 84%

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Margaritis

Channon

Antoniades

2014

Antioxidants & Redox Signaling

117

View full text Add to dashboard Cite

show abstract

“…Hussein et al demonstrated an additive antioxidant effect when valsartan was co-administered for 2 months to seven hypercholesterolaemic, hypertensive patients taking fluvastatin [40]. The Endothelial Protection, AT1 Blockade and Cholesterol-Dependent Oxidative Stress (EPAS) Trial demonstrated that treatment with pravastatin (40 mg/day), in 60 patients with stable coronary artery disease prior to elective coronary artery bypass grafting, was associated with an increase in the anti-atherosclerotic endothelial expression quotient Q, including mRNA expression (endothelial nitric oxide synthase and CNP divided by lectin-like oxidised LDL receptor-1, and gp91phox in left internal mammary arteries) [41]. Treatment with irbesartan (150 mg/day) had no significant effect.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment with irbesartan (150 mg/day) had no significant effect. However, when combined with pravastatin, it further increased lnQ, but a putative interaction of both therapies on lnQ was not significant [41]. Finally, the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) examined the effect of simvastatin treatment in 460 normocholesterolaemic patients [42].…”

Section: Discussionmentioning

confidence: 99%

The HMG-CoA reductase inhibitor rosuvastatin and the angiotensin receptor antagonist candesartan attenuate atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes via effects on advanced glycation, oxidative stress and inflammation

et al. 2008

View full text Add to dashboard Cite

Aims/hypothesis We evaluated the anti-atherosclerotic effect of the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, rosuvastatin, and the angiotensin II receptor blocker (ARB), candesartan, alone and in combination, in the streptozotocin-induced diabetic apolipoprotein Edeficient (Apoe −/− ) mouse. Methods Control and streptozotocin-induced diabetic Apoe −/− mice received rosuvastatin (5 mg kg −1 day −1 ), candesartan (2.5 mg kg −1 day −1 ), dual therapy or no treatment for 20 weeks. Aortic plaque deposition was assessed by Sudan IV staining and subsequent visual quantification. The abundance of proteins was measured using immunohistochemistry. Results Diabetes was associated with a fourfold increase in total plaque area. Rosuvastatin attenuated plaque area in diabetic mice in the absence of lipid-lowering effects. The anti-atherosclerotic effect of rosuvastatin was comparable to that observed with candesartan. A similar beneficial effect was seen with dual therapy, although it was not superior to monotherapy. Rosuvastatin treatment was associated with attenuated accumulation of AGE and AGE receptor (RAGE) in plaques. Similar beneficial effects on markers of oxidative stress were seen with the ARB and statin. Candesartan was more effective at reducing macrophage accumulation and collagen I abundance in plaques compared with rosuvastatin. The combined effect of candesartan and rosuvastatin was superior in reducing macrophage infiltration, monocyte chemoattractant protein-1 level, vascular AGE accumulation and RAGE abundance in the vascular wall. Furthermore, the combination tended to be more effective in reducing smooth muscle cell infiltration and connective tissue growth factor abundance in plaques. Conclusions/interpretation Rosuvastatin has direct antiatherosclerotic effects in diabetic macrovascular disease. These effects are independent of effects on lipids and comparable to the effects observed with candesartan.

show abstract

“…Measuring sLOX-1 may be a less invasive tool for the same purpose. In addition, sLOX-1 could be used to evaluate the therapeutic effects, such as administration of statins 38 or angiotensin II receptor blockers, 39 and body weight reduction, 40 because LOX-1 expression has been shown to be reduced by these interventions. However, in the present study plasma levels of sLOX-1 were comparable between patients with prehospital use of ACEI/ARB or statins and those without.…”

Section: 15-18mentioning

confidence: 99%

Soluble Lectin-Like Oxidized LDL Receptor-1 and High-Sensitivity Troponin T as Diagnostic Biomarkers for Acute Coronary Syndrome - Improved Values With Combination Usage in Emergency Rooms -

Kobayashi

Hata

Kume

et al. 2011

Circ J

View full text Add to dashboard Cite

Endothelial Protection, AT ₁ Blockade and Cholesterol-Dependent Oxidative Stress

Cited by 67 publications

References 38 publications

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

The HMG-CoA reductase inhibitor rosuvastatin and the angiotensin receptor antagonist candesartan attenuate atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes via effects on advanced glycation, oxidative stress and inflammation

Soluble Lectin-Like Oxidized LDL Receptor-1 and High-Sensitivity Troponin T as Diagnostic Biomarkers for Acute Coronary Syndrome - Improved Values With Combination Usage in Emergency Rooms -

Contact Info

Product

Resources

About

Endothelial Protection, AT 1 Blockade and Cholesterol-Dependent Oxidative Stress

Cited by 67 publications

References 38 publications

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

The HMG-CoA reductase inhibitor rosuvastatin and the angiotensin receptor antagonist candesartan attenuate atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes via effects on advanced glycation, oxidative stress and inflammation

Soluble Lectin-Like Oxidized LDL Receptor-1 and High-Sensitivity Troponin T as Diagnostic Biomarkers for Acute Coronary Syndrome - Improved Values With Combination Usage in Emergency Rooms -

Contact Info

Product

Resources

About

Endothelial Protection, AT ₁ Blockade and Cholesterol-Dependent Oxidative Stress