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

Linoleic acid enhances the secretion of plasminogen activator inhibitor type 1 by HepG2 cells.

This study was undertaken in order to assess whether triglycerides and/or their fatty acids directly influence the secretion of plasminogen activator inhibitor type 1 (PAI-1) in HepG2 cells. To this end, subconfluent HepG2 cells were incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16 h, and PAI-1 levels were determined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid composition at the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L) increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mumol/L). Incorporation of LA into cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [14C]LA. LA accumulated in all lipid classes including diacylglycerol, the incorporated LA being converted into arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid methyl esters. It is concluded that PAI-1 secretion in HepG2 cells is modulated by triacylglycerols and by linoleic acid and/or its metabolic products

The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation

Statin-induced inhibition of HMG-CoA reductase reduces cholesterol production and prevents the formation of many non-steroidal isoprenoid compounds, such as farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid attachments for the post-translational modification of various proteins, including the G-proteins and transcription factors involved in a number of cell processes. However, the blockade of isoprenylation elicited by statin treatment also has biological effects on cell function that go beyond the decrease in cholesterol synthesis: these are the so-called “pleiotropic” effects that mainly relate to vascular function. Endothelial dysfunction is an independent predictor of cardiovascular events that correlates with inflammation markers/mediators and robust predictors of cardiovascular diseases such as increased high-sensitivity C-reactive protein levels. The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide. This review describes the pleiotropic effects of statins that may be involved in modulating/preventing endothelial dysfunction and inflammatory processes, as well as the cellular and molecular mechanisms through which they improve endothelial function

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

Overall dietary variety and adherence to the Mediterranean diet show additive protective effects against coronary heart disease.

Abstract Background and aim Along with the increasing evidence of the cardioprotective effects of the Mediterranean Diet (MD), the scientific interest and advocacy of dietary variety as a potentially healthy eating habit gradually faded, until its complete oblivion in the latest European cardiovascular prevention guidelines. Our study aims to investigate whether dietary variety adds to the "Mediterranean-ness" of the diet in protecting against coronary heart disease (CHD). Methods and results In this case–control Italian study, data on eating habits were collected from 178 patients with CHD and 155 healthy controls, primarily males, frequency matched for age and gender, using the Food Frequency Questionnaire (FFQ) of the European Prospective Investigation into Cancer and Nutrition. Adherence to MD was estimated from FFQ by the Mediterranean Diet Score (MDS), an index developed by Trichopoulou (2003) ranging from 0 to 9, with higher scores indicating a stricter adherence. Overall dietary variety was computed from FFQ as a count of single food items consumed at least once a month. Associations between MDS or overall dietary variety and coronary status were evaluated by logistic regression models adjusted for BMI, physical activity, smoking, education, and caloric intake; the Odds Ratio (OR) for CHD for each 1.5-point increase in MDS was 0.76 [IC 95% 0.59; 0.98], whereas the OR for CHD for each 15-item increase in dietary variety was 0.62 [IC 95% 0.46; 0.84]. Remarkably, adherence to MD and overall dietary variety were independently associated with a significantly reduced chance of CHD. Conclusion Dietary Mediterranean-ness and overall dietary variety exhibit additive cardioprotective effects

8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature

Significance: 8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes). Recent Advances: Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD. Critical Issues: Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I2 = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls. Future Directions: 8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD. Antioxid. Redox Signal. 24, 548-555

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

Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction?

Coronary artery bypass surgery (CABG) is still one of the most frequently performed surgical procedures all over the world. The results of this procedure have been constantly improved over the years with low perioperative mortality rates, with relatively low complication rates. To further improve these outstanding results, the clinicians focused their attention at biomarkers as outcome predictors. Although biological testing for disease prediction has already been discussed many times, the role of biomarkers in outcome prediction after CABG is still controversial. In this article, we reviewed the current knowledge regarding the role of genetic and dynamic biomarkers and their possible association with the occurrence of adverse clinical outcomes after CABG. We also took into consideration that the molecular pathway activation and the possible imbalance may affect hard outcomes and graft patency. We analyzed biomarkers classified in two different categories depending on their possibility to change over time: genetic markers and dynamic markers. Moreover, we evaluated these markers by dividing them, into sub-categories, such as inflammation, hemostasis, renin-angiotensin, endothelial function, and other pathways. We showed that biomarkers might be associated with unfavorable outcomes after surgery, and in some cases improved outcome prediction. However, the identification of a specific panel of biomarkers or of some algorithms including biomarkers is still in an early developmental phase. Finally, larger studies are needed to analyze broad panel of biomarkers with the specific aim to evaluate the prediction of hard outcomes and graft patency