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BACKGROUND Heart failure is characterized by a tissue damage that progressively leads to mechanical cardiac dysfunction and remodeling. A recent investigation showed that α-1 antitripsin, an antiprotease, able to inhibit metalloproteinases, provides prognostic information about heart failure and mortality postacute myocardial infarction. Therefore, we conducted a study to establish if α-1 antitrypsin (AAT) could be considered a marker of severity of heart failure. METHODS A total of 182 heart failure patients (Group 1) were enrolled and AAT values were compared with controls (Group 2). RESULTS In Group 1 a significant increment of AAT levels respect to Group 2 was observed (P

It is commonly believed that the inactivation of inflammation is mainly due to the decay or cessation of inducers. In reality, in connection with the development of atherosclerosis, spontaneous decay of inducers is not observed. It is now known that lipid mediators originating from polyunsaturated fatty acids (PUFAs), which are important constituents of all cell membranes, can act in the inflamed tissue and bring it to resolution. In fact, PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are precursors to both pro-inflammatory and anti-inflammatory compounds. In this review, we describe the lipid mediators of vascular inflammation and resolution, and their biochemical activity. In addition, we highlight data from the literature that often show a worsening of atherosclerotic disease in subjects deficient in lipid mediators of inflammation resolution, and we also report on the anti-proteasic and anti-thrombotic properties of these same lipid mediators. It should be noted that despite promising data observed in both animal and in vitro studies, contradictory clinical results have been observed for omega-3 PUFAs. Many further studies will be required in order to clarify the observed conflicts, although lifestyle habits such as smoking or other biochemical factors may often influence the normal synthesis of lipid mediators of inflammation resolution.

Heart failure (HF) is considered one of the most common diseases and one of the major causes of death. The latest studies show that HF is associated with an increase in oxidative stress. The use of antioxidants as therapy is effective in animal models, but not in humans. In this review, we analyse some emerging markers related to oxidative stress, evaluating their possible use as therapeutic targets: galectin-3, a β galactoside associated with myocardial fibrosis, α1-antitrypsin, an antiprotease and lectin-like oxidized low-density-lipoprotein receptor-1, the major receptor for ox-LDL. The up-regulation of galectin-3 appears to be associated with HF, atrial fibrillation, dilated cardiomyopathy, fibrogenesis and mortality, while in other cases it seems that galectin-3 may be protective in ischaemia-reperfusion injury. Serum α1-antitrypsin protein levels may increase in the presence of high concentrations of serum proteases, which are over expressed during reperfusion. The overexpression of α1-antitrypsin or the exogenous α1-antitrypsin treatment exhibits an anti-oxidative stress role, evaluated by increased eNOS expression and by decreased MMP9 expression, implicated in HF. The cardiac lectin-like oxidized low-density-lipoprotein receptor-1 is activated by oxidative stress in ischaemia-reperfusion injury, inducing apoptosis in cardiomyocytes through the deleterious NF-kB pathway, while the administration of anti-lectin-like oxidized low-density-lipoprotein receptor-1 antibody suppresses apoptosis and reduces the extent of myocardial infarction. In conclusion, α1-antitrypsin and lectin-like oxidized low-density-lipoprotein receptor-1 seem to represent two good markers in HF and therapeutic targets, whereas galectin-3 does not.

Atherosclerosis is a systemic inflammation of the arteries characterized by atherosclerotic plaque due to the accumulation of lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins. Stable plaques present a chronic inflammatory infiltration, whereas vulnerable plaques present an ‘active’ inflammation involved in the thinning of the fibrous cap that predisposes to plaque rupture. Several complex biological cellular processes lead plaques to evolve from stable to vulnerable predisposing them to rupture and thrombosis. In this review, we analyze some emerging circulating biomarkers related to inflammation, ECM and lipid infiltration, angiogenesis, metalloproteinases and microRNA (miRNA), as possible diagnostic and prognostic indicators of plaque vulnerability.

Altered production of reactive oxygen species (ROS), causing lipid peroxidation and DNA damage, contributes to the progression of atherosclerosis and cancer. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a lectin-like receptor for oxidized low-density lipoproteins (ox-LDL) primarily expressed in endothelial cells and vasculature-rich organs. LOX-1 receptors is a marker for atherosclerosis, and once activated by ox-LDL or other ligands, stimulates the expression of adhesion molecules, pro-inflammatory signaling pathways and proangiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. Several different types of cancer reported LOX-1 gene upregulation, and numerous interplays exist concerning LOX-1 in atherosclerosis, metabolic diseases and cancer. One of them involves NF-kB, an oncogenic protein that regulates the transcription of several inflammatory genes response. In a model of cellular transformation, the MCF10A ER-Src, inhibition of LOX-1 gene reduces NF-kB activation and the inflammatory and hypoxia pathways, suggesting a mechanistic connection between cellular transformation and atherosclerosis. The remodeling proteins MMP-2 and MMP-9 have been found increased in angiogenesis in atherosclerotic plaque and also in human prostate cancer cells. In this review, we outlined the role of LOX-1 in atherogenesis and tumorigenesis as a potential link in these diseases, suggesting that LOX-1 inhibition could represent a promising strategy in the treatment of atherosclerosis and tumors.

Liposomes are one of the most studied and most promising nanocarriers to date, representing a biocompatible, safe, and efficient delivery system for both hydrophilic and lipophilic compounds.

Thyroid hormones (TH) play an important role in heart vascular system, and both hyperthyroidism and hypothyroidism are associated with altered cardiovascular system. Moreover, several evidences suggest that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels.

Several inflammatory factors have been determined as indicators of coronary artery disease (CAD) and recently some studies showed neutrophyl to lymphocyte ratio (NLR) as a powerful predictor. The aim of this study was to evaluate NLR, comparing it with the consolidate inflammatory and oxidative stress marker in a group of control and CAD patients. Twenty healthy subjects and 47 patients, that were affected by 1-4 compromised coronary arteries, were enrolled in the study. All subjects were classified into 3 groups on the base of NLR tertile. The efficacy of NLR as indicator of the severity of CAD and its association with inflammatory markers were analyzed. According to the tertile of NLR, patients in the high NLR value had higher % of males, number of compromise coronary arteries, CRP levels, neutrophyl count, and low lymphocyte count. Moreover NLR and CRP levels showed to be independent predictors of 3-4 compromised coronary arteries. The ROC curve analysis showed that CRP and NLR markers had the largest area under the curve (AUC = 0,85, 95% CI: 0,74-0,96, p = 0,000; AUC = 0,81, 95% CI: 0,66-0,96, p = 0,001). In conclusion our data indicate that only NLR and CRP are independent predictors for 3-4 compromised coronary arteries.

Studies from human and animal models with metabolic disease and hypertension highlight atrophic remodeling, reduced lumen size and thinner vascular walls of microvessels with profound density reduction. This impaired vascular response limits the perfusion of peripheral tissues inducing organ damage. These conditions are strongly associated with oxidative stress and in particular with the up-regulation of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Several factors such as cytokines, shear stress, and advanced glycation end-products, especially oxLDL, can up-regulate LOX-1. The activation of this receptor induces the production of adhesion molecules, cytokines and the release of reactive oxygen species via NADPH oxidase. LOX-1 is considered a potent mediator of endothelial dysfunction and it is significantly associated with reduced microvascular endothelium NO-dependent vasodilation in hypercholesterolemia and hypertension. Microvascular endothelial cells increased the expression of IL-6 in association with the increased concentration of LDL and its degree of oxidation. Moreover, increased IL-6 levels are associated with up-regulation of LOX-1 in a dose-dependent manner. Another consequence of microvascular inflammation is the generation of small amounts of ROS, similar to those induced by low concentration of oxLDL (

This study dealt with the effect of sourdough fermentation on antinutrients, phytochemicals, and antioxidant activities of flours from three Phaseoulus vulgaris L. genotypes with differing composition of lectins. Specifically, cultivar Lady Joy (LJ) devoid of phytohemagglutinin (PHA) and enriched in alfa-amylase inhibitor (αAI), breeding line P500 low in PHA and devoid of αAI, and Taylor's horticultivar, containing normal levels of both proteins. Sourdough fermentation positively affects the nutritional values of all bean flours by reducing some antinutrients, for example, phytic acid while preserving αAI activity. It significantly increased total polyphenols, flavonols, and ascorbic acid content, while reducing flavonoids. No significant differences in antioxidant activity, measured by in vitro and ex vivo assays on human erythrocytes, were found. The kinetic profiles of conjugated dienes analysis showed a strong inhibitory effect on low-density lipoproteins oxidation of all tested powders, with unfermented flours displaying the best antioxidant activity. Among bean powders, unfermented and fermented LJ showed the highest polyphenols level (4.21 ± 0.18 and 4.96 ± 0.15 mg GAE/g dw, respectively), oxygen radical absorbance capacity (ORAC) values (24.17 ± 0.14 and 24.02 ± 0.93 µmol TE/100g dw, respectively) and cellular antioxidant activity (71.6 ± 7.05 and 62.7 ± 3.3 units, respectively). Finally, since fermentation drastically reduces phytic acid content while preserving αAI activity, fermented LJ represents an important natural slimming supplement.

Cardiac Troponins (cTnI, cTnT), NT-proBNP, and galectin-3 (GAL-3) mirror cardiomyocyte injury, stretch, and fibrosis. However, although these biomarkers has been thoroughly studied in marathon or ultramarathon, the effects occurring running shorter distances, as half-marathon, are less known and data are generally limited to immediately post-race evaluation. Moreover, significant variation of alpha-1 antitrypsin (AAT), an anti-protease factor with anti-inflammatory properties, has been recently observed in heart failure, but not investigated in paraphysiological settings. The aim of the study was to evaluate these biomarkers concentration and trends in trained runners before half-marathon run and during a 48-h recovery period. In 18 half-marathon runners (15 males, 46 ± 6 years), cTnI, GAL-3 (Architect, Abbott), cTnT, NT-proBNP (Cobas e411, Roche), and AAT (Abcam, Cambridge, UK) were evaluated at rest, immediately post-run, and at 24 and 48-h recovery period. cTnT, NT-proBNP, and GAL-3 transiently increased after post-race, but normalized at 24 h (GAL-3 p

In the study of new drug molecules for the treatment of cancer, nitric oxide has received much attention for its tumoricidal role. In addition to its direct cytotoxic effect, NO may enhance the efficiency of classical chemotherapeutic drugs, resulting in a promising strategy against tumorigenesis and tumor progression. However, the clinical therapeutic potential of NO is limited by the short half-life, the concentration, and the biological microenvironment with which it interacts. Particular attention should be paid to the concentrations, as according to some authors, low NO levels could promote the growth of cancer cells. The development of a nanoparticle-based delivery system is aimed to the selective release of NO and drugs at the target tumor site, increasing their stability and biodistribution and preserving their therapeutic dosage. This review summarizes the current knowledge of NO-based anticancer treatments and their association with chemotherapy, focusing on the benefit of using nanotechnology.

This study focused on an extract from fermented flour from the Lady Joy variety of the common bean Phaseolus vulgaris. The extract, Lady Joy lysate (Lys LJ), is enriched in antioxidant compounds during the fermentation. We assessed it for its protective effect on endothelial cells treated with oxidized-LDL (ox-LDL). The oxidative stress was determined by measuring the contents of thiobarbituric acid-reactive substances and reactive oxygen metabolites. ICAM-1, ET-1 and IL-6 concentrations were assessed using ELISA. LOX-1 and CHOP expression were analyzed using both quantitative RT-PCR and ELISA or western blotting. Ox-LDL treatment induced significant oxidative stress, which was strongly reduced by pre-treatment with the extract. The ox-LDL exposure significantly enhanced ICAM-1, IL-6 and ET-1 levels over basal levels. Lys LJ pre-treatment exerted an inhibitory effect on ox-LDL-induced endothelial activation with ICAM-1 levels comparable to those for the untreated cells. IL-6 and ET-1 production, although reduced, was still significantly higher than for the control. Both LOX-1 and CHOP expression were upregulated after ox-LDL exposure, but this effect was significantly decreased after Lys LJ pre-treatment. Lys LJ alone did not alter the ICAM-1, IL-6 and ET-1 concentrations or CHOP expression, but it did significantly lower the LOX-1 protein level. Our data suggest that Lys LJ is an effective antioxidant that is able to inhibit the oxidation process, but that it is only marginally active against inflammation and ET-1 production in HMEC-1 exposed to ox-LDL.