Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels

Mercuro, Giuseppe; Zoncu, Sandra; Saiu, Francesca; Sarais, Cristiano; Rosano, Giuseppe M.C.

doi:10.1016/s0002-9149(02)02602-4

Cited by 29 publications

(16 citation statements)

References 6 publications

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“…Statin treatment has also been shown to improve endothelial-dependent peripheral artery vasodilation (Mercuro et al, 2002). Here we show for the first time that simvastatin attenuates diabetes-induced coronary endothelial dysfunction and significantly improves ACh-mediated vasorelaxation.…”

Section: Discussionmentioning

confidence: 53%

Simvastatin Improves Diabetes-Induced Coronary Endothelial Dysfunction

Tawfik

El-Remessy

Matragoon

et al. 2006

J Pharmacol Exp Ther

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3-Hydroxy-3-methylglutaryl CoA reductase inhibitors decrease cardiovascular morbidity in diabetic patients, but the mechanism is unclear. We studied the actions of simvastatin (SIM) in enhancing NO bioavailability and reducing oxidative stress in coronary vessels from diabetic rats and in rat coronary artery endothelial cells (RCAEC) exposed to high glucose. Coronary arteries isolated from diabetic rats showed decreases in acetylcholine (ACh)-mediated maximal relaxation from 81.0 Ϯ 4.5% in controls to 43.5 Ϯ 7.6% at 4 weeks and 22.3 Ϯ 0.6% at 10 weeks of diabetes. This effect was associated with oxidative stress in coronary vessels as shown by dichlorofluorescein (DCF) imaging and nitrotyrosine labeling. Diabetes also reduced trans-coronary uptake of [ 3 H]L-arginine. Supplemental L-arginine (50 mg/kg/day p.o.) did not improve coronary vasorelaxation to ACh. However, SIM treatment (5 mg/kg/day subcutaneously) improved maximal ACh relaxation to 65.8 Ϯ 5.1% at 4 weeks and 47.1 Ϯ 3.9% at 10 weeks. Coronary arteries from rats treated with both SIM and L-arginine demonstrated the same maximal relaxation to ACh (66.1 Ϯ 3%) as SIM alone. Mevalonate and L-NAME (N -nitro-L-arginine methyl ester hydrochloride) inhibited the response to ACh in SIM-treated diabetic rats. Coronary arteries from all groups relaxed similarly to sodium nitroprusside. SIM increased endothelial NO synthase protein levels and blocked diabetes-induced increases in DCF and nitrotyrosine labeling in diabetic coronary vessels. SIM treatment restored normal NO levels in media from high-glucosetreated RCAEC and plasma of diabetic rat. Treatment with SIM or the NADPH oxidase inhibitor apocynin also blocked high-glucoseinduced increases in reactive oxygen species and superoxide formation in RCAEC. Taken together, these data suggest that SIM improves diabetes-induced coronary dysfunction by reducing oxidative stress and increasing NO bioavailability.

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Section: Discussionmentioning

confidence: 53%

Simvastatin Improves Diabetes-Induced Coronary Endothelial Dysfunction

Tawfik

El-Remessy

Matragoon

et al. 2006

J Pharmacol Exp Ther

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“…First, variable definitions of menopausal status were used. [27][28][29][30][31] It is also likely that changes in lipids gradually reflect the ongoing decline in ovarian function. 32 Second, regulation of plasma TGs in premenopausal and postmenopausal women may differ.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Natural Menopause on Postprandial Lipemia in Heterozygotes for Familial Hypercholesterolemia

Kolovou

Anagnostopoulou

Pilatis

et al. 2004

Journal of Women's Health

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“…This is a crucial issue because although aspirin, 37 angiotensin-converting enzyme inhibitors, 38 and statins 39 improve endothelial function and reduce cardiovascular morbidity and mortality, 40 -42 antioxidants (in some studies 43 ) and hormone replacement therapy, 44 at least during acute administration, also improve endothelial function but have either neutral 42,45 or negative 46 effects on clinical outcomes. Thus, studies designed to correlate improvement in endothelial function with improvement in outcome are needed to convince us that normalization of function with repeated measurements is an appropriate strategy in management of patients with endothelial dysfunction.…”

Section: Unresolved Issues Controversies and Future Directionsmentioning

confidence: 99%

Surrogate Markers for Cardiovascular Disease

et al. 2004

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The endothelium constitutes the largest organ system in the body. "Endothelial function" refers to a multitude of physiological functions of the vascular endothelium that are achieved via secretion of diverse bioactive substances. This renders the endothelium an active participant in healthy homeostasis of the vascular wall that includes normal vasomotion, inhibition of platelet aggregation and thrombus generation, and maintenance of relative impermeability. Cardiovascular risk factors activate a number of pro-oxidative genes in the vascular wall resulting in generation of reactive oxygen species that ultimately promote endothelial release of transcriptional and growth factors, proinflammatory cytokines, chemoattractant substances, and adhesion molecules. [1][2][3] This complex cascade of events underlies the transition from normal endothelial function to endothelial dysfunction. One of the earliest manifestations of increased vascular oxidant stress is the reduced bioavailability of nitric oxide (NO) as a result of inhibition and uncoupling of endothelial NO synthase, the enzyme responsible for generation of NO, and from rapid catabolism of available NO by reactive oxygen species to peroxynitrite and hydrogen peroxide that can further amplify vascular oxidative stress. The resulting functional consequences include abnormal vasomotor activity, development of a procoagulant endothelial surface, inflammation, and, ultimately, plaque formation. Clinical measurements of endothelium-dependent vasodilation (NO-mediated process) by a variety of different techniques provide a marker of endothelial integrity.Almost all conventional risk factors for atherosclerosis are associated with endothelial dysfunction. These include sedentary lifestyle and obesity, hypercholesterolemia, hypertension, diabetes, insulin resistance, smoking, and aging. The extent of endothelial dysfunction appears to correlate with the traditional risk factor "burden," thus implying that combined or repeated injury to the vascular endothelium results in greater dysfunction. Nevertheless, there is considerable heterogeneity in the magnitude of dysfunction observed in individuals with similar risk factor profiles. 4,5 Novel risk factors such as infections, hyperhomocystinemia, genetic heterogeneity, and the variable duration of exposure to individual risk factors presumably account for some of this observed variability. Moreover, evidence now suggests that endothelial function may be modulated not only by factors causing vascular injury but also by repair mechanisms, potentially mediated via circulating endothelial progenitor cells. 6 Thus, the concept has been put forth that endothelial vasodilator function is a reflection of overall vascular health, or a barometer of the injury/repair inflicted by multiple environmental and genetic factors, and, therefore, could potentially serve as a useful diagnostic and prognostic tool in individual patients.It is important to realize that the presence of a similar risk factor profile does not necessarily imply the...

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Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels

Cited by 29 publications

References 6 publications

Simvastatin Improves Diabetes-Induced Coronary Endothelial Dysfunction

Simvastatin Improves Diabetes-Induced Coronary Endothelial Dysfunction

The Influence of Natural Menopause on Postprandial Lipemia in Heterozygotes for Familial Hypercholesterolemia

Surrogate Markers for Cardiovascular Disease

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