Publications (18) View all
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Article: Interactions between Vascular Wall and Perivascular Adipose Tissue Reveal Novel Roles for Adiponectin in the Regulation of eNOS Function in Human Vessels.
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ABSTRACT: BACKGROUND: Adiponectin (AdN) is an adipokine with potentially important roles in human cardiovascular disease states. We studied the role of AdN in the cross-talk between adipose tissue (AT) and vascular redox state in patients with atherosclerosis. METHODS AND RESULTS: The study included 677 patients undergoing coronary bypass surgery (CABG). Endothelial function was evaluated by flow mediated dilation of the brachial artery in vivo and by vasomotor studies in saphenous vein (SV) segments ex vivo. Vascular superoxide (O2(-)) and eNOS uncoupling were quantified in SV and internal mammary artery (IMA) segments. Local AdN gene expression and ex vivo release were quantified in peri-vascular (peri-SV and peri-IMA), subcutaneous and mesothoracic AT from 248 patients. Circulating AdN was independently associated with nitric oxide (NO) bioavailability and O2(-) production/eNOS uncoupling in both arteries and veins. These findings were supported by a similar association between functional polymorphisms in the AdN gene and vascular redox state. By contrast, local AdN gene expression/release in perivascular AT was positively correlated with O2(-) and eNOS uncoupling in the underlying vessels. In ex vivo experiments with human SVs and IMAs, AdN induced Akt-mediated eNOS phosphorylation and increased tetrahydrobiopterin bioavailability, improving eNOS coupling. In ex vivo experiments with human SVs/IMAs and AT, we demonstrated that peroxidation products produced in the vascular wall (i.e., 4-hydroxynonenal) up-regulate AdN gene expression in perivascular AT via a PPAR-γ-dependent mechanism. CONCLUSIONS: We demonstrate for the first time that AdN improves the redox state in human vessels by restoring eNOS coupling, and identify a novel role of vascular oxidative stress in the regulation of AdN expression in human perivascular adipose tissue.Circulation 04/2013; · 14.74 Impact Factor -
Article: Artifactual elevation of plasma sCD40L by residual platelets in patients with coronary artery disease.
International journal of cardiology 04/2013; · 7.08 Impact Factor -
Article: Heparin administration leads to rapid decrease in plasma matrix metalloproteinase-9.
International journal of cardiology 07/2012; · 7.08 Impact Factor -
Article: Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations.
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ABSTRACT: Oxidative stress is a key feature in atherogenesis, since reactive oxygen species (ROS) are involved in all stages of the disease, from endothelial dysfunction to atheromatic plaque formation and rupture. It is therefore important to identify reliable biomarkers allowing us to monitor vascular oxidative stress status. These may lead to improved understanding of disease pathogenesis and development of new therapeutic strategies. Measurement of circulating biomarkers of oxidative stress is challenging, since circulation usually behaves as a separate compartment to the individual structures of the vascular wall. However, measurement of stable products released by the reaction of ROS and vascular/circulating molecular structures is a particularly popular approach. Serum lipid hydroperoxides, plasma malondialdehyde or urine F2-isoprostanes are widely used and have a prognostic value in cardiovascular disease. Quantification of oxidative stress at a tissue level is much more accurate. Various chemiluminescence and high performance liquid chromatography assays have been developed over the last few years, and some of them are extremely accurate and specific. Electron spin resonance spectroscopy and micro-electrode assays able to detect ROS directly are also widely used. In conclusion, measurement of circulating biomarkers of oxidative stress is valuable, and some of them appear to have predictive value in cardiovascular disease. However, these biomarkers do not necessarily reflect intravascular oxidative stress and therefore cannot be used as therapeutic targets or markers to monitor pharmacological treatments in clinical settings. Measurement of vascular oxidative stress status is still the only reliable way to evaluate the involvement of oxidative stress in atherogenesis.Current Medicinal Chemistry 04/2012; 19(16):2504-20. · 4.86 Impact Factor -
Article: Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials.
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ABSTRACT: Ample evidence exists in support of the potent anti-inflammatory properties of statins. In cell studies and animal models statins exert beneficial cardiovascular effects. By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation, favorably modulate vascular and myocardial redox state and improve nitric oxide bioavailability. Randomized clinical trials have demonstrated that further to their lipid lowering effects, statins are useful in the primary and secondary prevention of coronary heart disease (CHD) due to their anti-inflammatory potential. The landmark JUPITER trial suggested that in subjects without CHD, suppression of low-grade inflammation by statins improves clinical outcome. However, recent trials have failed to document any clinical benefit with statins in high risk groups, such in heart failure or chronic kidney disease patients. In this review, we aim to summarize the existing evidence on statins as an anti-inflammatory agent in atherogenesis. We describe the molecular mechanisms responsible for the antiinflammatory effects of statins, as well as clinical data on the non lipid-lowering, anti-inflammatory effects of statins on cardiovascular outcomes. Lastly, the controversy of the recent large randomized clinical trials and the issue of statin withdrawal are also discussed.Current pharmaceutical design 02/2012; 18(11):1519-30. · 4.41 Impact Factor
