Depressive and anxiety symptoms screening in cardiac inpatients : a virtuous italian approach to psychocardiology

Despite the fact that American Heart Association (AHA) recommended a systematic screening for depression in cardiovascular inpatients, poor attention has been given to this issue. Furthermore, no specific guidelines exist for anxiety screening in cardiovascular inpatients. Thus, the aims of this study were to verify the feasibility of a depressive and anxiety symptoms screening protocol in an Italian hospital specializing in cardiovascular diseases and to evaluate both anxiety and depressive symptoms prevalence. A group of 2009 consecutive inpatients completed the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7). The rates of depressive and anxiety symptoms were almost 9% and 16% respectively. Men were less likely than women to experience both depressive and anxiety symptoms. Patients who were admitted to the heart failure unit reported higher risk of experiencing both symptoms compared to patients in other wards. Similarly, patients admitted to the cardiac surgery unit showed a higher risk of experiencing anxiety symptoms compared to other patients. The proposed screening procedure showed a good feasibility and acceptance. This study highlighted the importance of implementing a short screening procedure in hospitals dealing with cardiovascular inpatients to identify those individuals who require specific attention and interventions

Protein-Kinase-C inhibitors and gemfibrozil prevent the enhancing effect of very low density lipoproteins on the biosynthesis of plasminogen activator inhibitor type 1 by HepG2 cells

Triglyceride-rich lipoproteins (VLDL) have been previously shown to enhance the biosynthesis of plasminogen activator inhibitor type 1 (PAl-1) by HepG2 cells. This study was undertaken to assess whether the effect of VLDL on PAI-1 antigen and mRNA induction could be by protein kinase C (PKC) signaling pathway. To this end confluent HepG2 cells were first incubated for 16 h with VLDL isolated from normal donors, at the 100 \ub5g/ml concentration with or without inhibitors of PKC. At the end of incubation PAI-1 antigen released in the conditioned medium was determined by ELISA and PAI-1 mRNA expression was assessed by Northern analysis. Exposure of HepG2 cells to 100 \ub5g/ml VLDL resulted in a twofold increase in PAI-1 antigen release and total PAI-1 mRNA expression. H7 (50 11M) and sphingosine (3-5 \ub5M) almost completely prevented (> 80%) the effect of VLDL on PAI-1 antigen release and total PAI-1 mRNA accumulation. In addition down regulation of PKC, obtained by preincubation of HepG2 cells with PMA (100 nM) for 24h, prevented the effect of VLDL on PAI-1 biosynthesis. Established that the effect of VLDL on PAI-1 biosynthesis was mediated by activation of PKC signaling pathway we evaluated whether fibric acid derivatives influenced PAI-1 biosynthesis in unstimulated HepG2 cells and in cells exposed to VLDL. In unstimulated HepG2 cells, Gemfibrozil (0.1-0.75 mM) significantly reduced PAI-1 antigen release (-85% at the 0.75 mM concentration) and mRNA expression, whereas Bezafibrate at the highest concentration used (1 mM) reduced PAI-1 antigen release by 20%, with no effect on PAI-1 mRNA expression. In VLDL treated cells, only Gemfibrozil, at the 0 .75 mM concentration, attenuated (-50%) the biosynthesis of PAI-1 as induced by VLDL (100 \ub5g/ml) . It is concluded that VLDL enhance PAI-1 biosynthesis through activation of PKC and that Gemfibrozil, but not Bezafibrate, attenuates PAI-1 induction in these cells

Biology and Role of Extracellular Vesicles (EVs) in the Pathogenesis of Thrombosis

Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications

Physical Exercise Affects Adipose Tissue Profile and Prevents Arterial Thrombosis in BDNF Val66Met Mice

Adipose tissue accumulation is an independent and modifiable risk factor for cardiovascular disease (CVD). The recent CVD European Guidelines strongly recommend regular physical exercise (PE) as a management strategy for prevention and treatment of CVD associated with metabolic disorders and obesity. Although mutations as well as common genetic variants, including the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, are associated with increased body weight, eating and neuropsychiatric disorders, and myocardial infarction, the effect of this polymorphism on adipose tissue accumulation and regulation as well as its relation to obesity/thrombosis remains to be elucidated. Here, we showed that white adipose tissue (WAT) of humanized knock-in BDNFVal66Met (BDNFMet/Met) mice is characterized by an altered morphology and an enhanced inflammatory profile compared to wild-type BDNFVal/Val. Four weeks of voluntary PE restored the adipocyte size distribution, counteracted the inflammatory profile of adipose tissue, and prevented the prothrombotic phenotype displayed, per se, by BDNFMet/Met mice. C3H10T1/2 cells treated with the Pro-BDNFMet peptide well recapitulated the gene alterations observed in BDNFMet/Met WAT mice. In conclusion, these data indicate the strong impact of lifestyle, in particular of the beneficial effect of PE, on the management of arterial thrombosis and inflammation associated with obesity in relation to the specific BDNF Val66Met mutation

Relationship between haemostatic variables and the progression of carotid atherosclerosis

Increases in the thickness of common carotid intima-media (CC-IMT), as measured by B-mode ultrasonography, have been widely used in both population studies and clinical trials in the search for risk factors for early atherosclerosis progression. In this study we have investigated the relations between several baseline haemostatic and conventional risk factors and CC-IMT changes over 16 months in 64 peripheral arterial disease (PAD) patients, randomly selected from the prospective PLAT study series. Samples from 24 (37.5%) patients who showed increases in CC-IMT during the follow-up period were compared with those from 40 (62.5%) in which CC-IMT remained unchanged. Baseline conventional risk factors and coagulation variables were similar in the two groups except for higher plasma concentrations of von Willebrand factor (vWF) (178.3\ub153.6 vs 141.2\ub153.7 SD%, p=0.01) and Factor VII (FVII) (133 .9\ub136.4 vs 107.0\ub127.3, p=0.001) in the patients with increased CC-IMT. CC-IMT increases correlated positively with plasma levels of FVII (r=0 .31, p<0.01) and vWF (r=0.31, p<0.31 ). Multiple stepwise regression analysis identified FVII as the only independent variable associated with an increase in CC-IMT (\uf062=0.83 p<0.01). Thus, high plasma concentration of FVII and vWF may be associated with the progression of early carotid atherosclerosis in PAD patients

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

Cysteinyl leukotrienes (CysLTs) are potent lipid mediators widely known for their actions in asthma and in allergic rhinitis. Accumulating data highlights their involvement in a broader range of inflammation-associated diseases such as cancer, atopic dermatitis, rheumatoid arthritis, and cardiovascular diseases. The reported elevated levels of CysLTs in acute and chronic brain lesions, the association between the genetic polymorphisms in the LTs biosynthesis pathways and the risk of cerebral pathological events, and the evidence from animal models link also CysLTs and brain diseases. This review will give an overview of how far research has gone into the evaluation of the role of CysLTs in the most prevalent neurodegenerative disorders (ischemia, Alzheimer's and Parkinson's diseases, multiple sclerosis/experimental autoimmune encephalomyelitis, and epilepsy) in order to understand the underlying mechanism by which they might be central in the disease progression

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