Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages

Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7beta-hydroxycholesterol, and 7-oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid-containing phospholipids, produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis

In vitro measurement of platelet glycoprotein IIb/IIIa receptor blockade by abciximab: interindividual variation and increased platelet secretion

Inhibition of soluble fibrinogen binding to activated platelets represents the target of pharmacologic approach with antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. In this study we assessed the effects of abciximab, a recombinant chimeric Fab fraction of the antibody against GPIIb/IIIa, on several markers of platelet activation

Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases

Cysteinyl leukotrienes (CysLTs) are potent lipid inflammatory mediators synthesized from arachidonic acid, through the 5-lipoxygenase (5-LO) pathway. Owing to their properties, CysLTs play a crucial role in the pathogenesis of inflammation; therefore, CysLT modifiers as synthesis inhibitors or receptor antagonists, central in asthma management, may become a potential target for the treatment of other inflammatory diseases such as the cardiovascular disorders. 5-LO pathway activation and increased expression of its mediators and receptors are found in cardiovascular diseases. Moreover, the cardioprotective effects observed by using CysLT modifiers are promising and contribute to elucidate the link between CysLTs and cardiovascular disease. The aim of this review is to summarize the state of present research about the role of the CysLTs in the pathogenesis and progression of atherosclerosis and myocardial infarction

Patho- physiological role of BDNF in fibrin clotting

Circulating levels of Brain Derived Neurotrophic Factor (BDNF) are lower in coronary heart disease (CHD) than in healthy subjects and are associated with coronary events and mortality. However, the mechanism(s) underling this association is not fully understood. We hypothesize that BDNF may influence fibrin fiber structure and clot stability, favoring clot lysis and thrombus resolution. We showed that recombinant BDNF (rh-BDNF) influenced with clot formation in a concentration-dependent manner in both purified fibrinogen and plasma from healthy subjects. In particular, rh-BDNF reduced the density of fibrin fibers, the maximum clot firmness (MCF) and the maximum clot turbidity, and affected the lysis of clot. In addition, both thrombin and reptilase clotting time were prolonged by rh-BDNF, despite the amount of thrombin formed was greater. Intriguingly, CHD patients had lower levels of BDNF, greater fibrin fibers density, higher MCF than control subjects, and a negative correlation between BDNF and MCF was found. Of note, rh-BDNF markedly modified fibrin clot profile restoring physiological clot morphology in CHD plasma. In conclusion, we provide evidence that low levels of BDNF correlate with the formation of bigger thrombi (in vitro) and that this effect is mediated, at least partially, by the alteration of fibrin fibers formation

Reproducibility validation study comparing analog and digital imaging technologies for the measurement of intima-media thickness

New advances in B-mode imaging technologies have led to improved quality in the detection of minute changes in the surface of intima-media thickness (IMT) and plaques. The new digital systems, with increased numbers of imaging channels, multiple frequency probes, and increased microprocessing speeds, now generate images comparable to those of the analog predecessors. Can these digital systems have reproducibility comparable to that of a pure analog system? We compared the Biosound 2000II (analog) system with the Esaote AU4 (digital) system

Trials in "true" dyslipidemic patients are urged to reconsider comprehensive lipid management as a means to reduce residual cardiovascular risk

Randomized cardiovascular trials aimed to reduce the excessive residual risk in high-risk patients through a more aggressive LDL-cholesterol control or targeting triglycerides or HDL-cholesterol levels have shown a null or, at best, limited incremental benefit. In some cases, the treatment produced meaningful effects only in study subgroups. As a consequence, some compounds were withdrawn (e.g. nicotinic acid derivatives and CETP inhibitors), whereas others (fibrates) are utilized with reluctance due to the low level of evidence-based data. By reviewing these trials analytically, we identified a common feature that might explain their meagre results: most of them involved patients generically at high cardiovascular risk with normal or near normal lipid levels and not patients with "true" dyslipidemia, who would receive the treatment if it were part of usual care. These observations may warrant reexamining a central criterion of pragmatism, eligibility, in the outline of forthcoming cardiovascular trials with novel lipid-modifying drugs

Corrigendum to “Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model”

In the article titled "Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model" [1], references [2, 3] should have been included as references 24 and 25 in the original article. Accordingly, in the introduction section, the text reading "Echocardiographically, MVP is defined as a single or bileaflet prolapse, at least 2mm beyond the long-axis annular plane, while the assessment of valve regurgitation takes into account the effective regurgitant orifice area (EROA) [2]" should be changed to "Echocardiographically, MVP is defined as a single or bileaflet prolapse, at least 2 mm beyond the long-axis annular plane, while the assessment of the severity of MR relies on several parameters according to the current recommendations [24, 25]." Additionally, the Acknowledgments section should be updated as follows: "The authors thank the entire Cardiac Surgery Unit at Centro Cardiologico Monzino for the clinical data and blood collection. The authors also would like to thank Dr. Paola Gripari for patient evaluation and critical review. This work was supported by the Fondazione Gigi e Pupa FerrariONLUS and the Italian Ministry of Health [RC2015-BIO30-2613051 to Centro CardiologicoMonzino].