M1 and M2 macrophage proteolytic and angiogenic profile analysis in atherosclerotic patients reveals a distinctive profile in type 2 diabetes.

This study aimed to investigate atherosclerotic mediators' expression levels in M1 and M2 macrophages and to focus on the influence of diabetes on M1/M2 profiles. Macrophages from 36 atherosclerotic patients (19 diabetics and 17 non-diabetics) were cultured with interleukin-1β (IL-1β) or IL-4 to induce M1 or M2 phenotype, respectively. The atherosclerotic mediators' expression was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR).

Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions.

Rationale: Percutaneous aortic valve procedures are a major breakthrough in the management of patients with aortic stenosis. Residual gradient and residual aortic regurgitation are major predictors of midterm and long-term outcome after percutaneous aortic valve procedures. We hypothesized that (1) induction/recovery of high molecular weight (HMW) multimers of von Willebrand factor defect could be instantaneous after acute changes in blood flow, (2) a bedside point-of-care assay (platelet function analyzer-closure time adenine DI-phosphate [PFA-CADP]), reflecting HMW multimers changes, could be used to monitor in real-time percutaneous aortic valve procedures.

Successful orthotopic transplantation of short tracheal segments without immunosuppressive therapy.

Objectives: Results of tracheal transplantation have been disappointing due to of ischaemia and rejection. It has been experimentally demonstrated that results of tracheal autograft/allograft transplantation were correlated with both graft length and revascularization method. Recently, we demonstrated that heterotopic epithelium-denuded-cryopreserved tracheal allograft (TA) displayed satisfactory immune tolerance.

Alterations in neutrophil production and function at an early stage in the high-fructose rat model of metabolic syndrome.

Background: Although neutrophils are crucially involved in inflammation, they have received only little attention in metabolic syndrome (MetS). We hypothesized that neutrophil infiltration into adipose tissue (AT) may occur at an early stage of MetS, in association with modulation of major functions of neutrophils and of their bone marrow production.

Methods: Fifty-six male Sprague-Dawley rats were fed regular (control rats (CRs)) or high-fructose (60%; fructose-fed rats (FFRs)) diets.

Immune tolerance of epithelium-denuded-cryopreserved tracheal allograft.

Objectives: Animal and clinical studies have demonstrated the feasibility of tracheal allograft transplantation after a revascularization period in heterotopy, thus requiring immunosuppressive therapy. Given the key role of the respiratory epithelium in the immune rejection, we investigated the consequence of both epithelium denudation and cryopreservation in immune tolerance of tracheal allograft in a novel rabbit model.

Methods: Five adult female New Zealand rabbits served as donors of tracheas that were denuded of their epithelium and then cryopreserved, and 13 males were used as recipients.

Liver X receptor activation stimulates iron export in human alternative macrophages.

Rationale: In atherosclerotic plaques, iron preferentially accumulates in macrophages where it can exert pro-oxidant activities.

Objective: The objective of this study was, first, to better characterize the iron distribution and metabolism in macrophage subpopulations in human atherosclerotic plaques and, second, to determine whether iron homeostasis is under the control of nuclear receptors, such as the liver X receptors (LXRs).

Methods And Results: Here we report that iron depots accumulate in human atherosclerotic plaque areas enriched in CD68 and mannose receptor (MR)-positive (CD68(+)MR(+)) alternative M2 macrophages.

Identification of additional proteins in differential proteomics using protein interaction networks.

In this study, we developed a novel computational approach based on protein-protein interaction networks to identify a list of proteins that might have remained undetected in differential proteomic profiling experiments. We tested our computational approach on two sets of human smooth muscle cell protein extracts that were affected differently by DNase I treatment. Differential proteomic analysis by saturation DIGE resulted in the identification of 41 human proteins.

Tracheal reconstruction with a composite graft: fascial flap-wrapped allogenic aorta with external cartilage-ring support.

Objectives: Animal and clinical studies have demonstrated the feasibility of tracheal replacement by silicone-stented allogenic aortas. In clinical trials, however, this graft did not show mature cartilage regeneration into the grafts as was observed in animal models. To solve this issue, we investigated tracheal replacement with a composite graft based on a fascial flap-wrapped allogenic aorta with external cartilage-ring support in a rabbit model.

Quantitative mass spectrometry analysis using PAcIFIC for the identification of plasma diagnostic biomarkers for abdominal aortic aneurysm.

Background: Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1-4% mortality occurring on rupture in males older than 65 years.

Measuring and targeting aldosterone and renin in atherosclerosis-a review of clinical data.

Our understanding of the development and progression of atherosclerosis has increased substantially over the past decades. A significant role for the renin-angiotensin-aldosterone system (RAAS) in this process has gained appreciation in recent years. Preclinical and clinical studies have associated components of the RAAS with various cardiovascular disease conditions.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

Background: Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI.

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction.

Background: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction.

Method And Results: One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male).

Prognostic value of hemoglobin decline over the GRACE score in patients hospitalized for an acute coronary syndrome.

In this work, we analyzed the prognostic significance of changes in hemoglobin during intensive care unit (ICU) stay in patients with acute coronary syndromes (ACS). We prospectively enrolled 591 patients (62 ± 14 years old, 73% male, 48% ST elevated myocardial infarction) free of blood cell transfusion or bleeding events. Changes in hemoglobin between admission and ICU discharge were obtained.

Renal resistance index and its prognostic significance in patients with heart failure with preserved ejection fraction.

Background: Functional renal impairment is a common feature of heart failure with preserved ejection fraction (HFpEF). The link between functional renal impairment and HFpEF remains incompletely understood. With hypertension and diabetes as frequent co-morbidities, patients with HFpEF are at risk of developing intra-renal vascular hemodynamic alterations that may lead to functional renal impairment and impact on prognosis.

Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARγ and LXRα pathways.

Rationale: A crucial step in atherogenesis is the infiltration of the subendothelial space of large arteries by monocytes where they differentiate into macrophages and transform into lipid-loaded foam cells. Macrophages are heterogeneous cells that adapt their response to environmental cytokines. Th1 cytokines promote monocyte differentiation into M1 macrophages, whereas Th2 cytokines trigger an "alternative" M2 phenotype.

Inferior vena cava agenesis and deep vein thrombosis: 10 patients and review of the literature.

Inferior vena cava agenesis (IVCA) is a rare condition, found in almost 5% of patients under 30 years old with unprovoked deep venous thrombosis (DVT). We describe 10 consecutive patients with IVCA-associated DVT and conducted an extensive literature review to investigate the typical spectrum of IVCA-associated DVT. Among our patients (eight men and two women; mean age, 25 ± 4.

The presence of apoptotic bone marrow cells impairs the efficacy of cardiac cell therapy.

Injection of autologous bone marrow cells into infarcted myocardium has been proposed to limit the deterioration of cardiac function following myocardial infarction (MI); unfortunately, the beneficial effects observed have been modest. One of the limiting factors is believed to be poor local survival of the injected cells, but the potential impact of apoptosis among the injected cells has yet to be assessed. Therefore, this study aimed to quantify the apoptosis rate in bone marrow mononuclear cells (BMMCs) prepared for cardiac therapy, and to analyze their effects in vitro on cardiomyoblast apoptosis and in vivo on cardiac function recovery following MI.

Atherosclerotic-like process in aortic stenosis: activation of the tissue factor-thrombin pathway and potential role through osteopontin alteration.

Background: We recently demonstrated in an experimental model the expression of tissue factor (TF) in aortic valves. Thrombin, generated at the end of the TF-initiated coagulation cascade, has been shown to cleave the anti-calcific osteopontin (OSP) liberating the pro-inflammatory OSP N-half.

Objectives: We hypothesized that TF might play an important role in calcific aortic valve stenosis (AS) through thrombin generation and hence evaluated the valvular expression of TF and its inhibitor (TF pathway inhibitor), α-thrombin, OSP and its thrombin-cleaved form (OSP N-half).

Impact of valvuloarterial impedance on left ventricular longitudinal deformation in patients with aortic valve stenosis and preserved ejection fraction.

Background: Left ventricular (LV) longitudinal deformation is a good marker of intrinsic myocardial dysfunction in pressure overload cardiomyopathies.

Aim: To assess the effect of valvuloarterial haemodynamic load on LV longitudinal deformation in patients with aortic valve stenosis (AVS) and preserved LV ejection fraction (LVEF).

Methods: Global LV longitudinal strain (GLS) was measured using speckle tracking imaging in a series of 82 consecutive patients with AVS (mean age 75+/-10 years; 50% men).

Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation.

Objectives: The objective of the study was to determine the prevalence of bleeding during continuous-flow left ventricular assist device support and to identify potential mechanisms for those bleeding events.

Background: Bleeding is frequently reported with continuous-flow left ventricular assist devices and may result from anticoagulation coupled with bleeding diathesis such as acquired von Willebrand syndrome. Accordingly, the prevalence of coagulation abnormalities including laboratory assessment for von Willebrand syndrome, bleeding events during device support, and at heart transplantation were evaluated.

Frequency of abdominal aortic aneurysm in patients undergoing coronary artery bypass grafting.

The aims of this study were to clarify the prevalence and the risk factors for unsuspected abdominal aortic aneurysm (AAA) in patients who underwent coronary artery bypass grafting for severe coronary artery disease and to identify the most at risk patients for AAA. Among 217 patients (189 men, mean age 64 +/- 11 years), asymptomatic AAAs, as prospectively identified by echocardiography, were found in 15 patients (6.9%).