Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction.

Rationale: The extracellular matrix may induce detrimental inflammatory responses on degradation, causing adverse cardiac remodeling and heart failure. The extracellular matrix protein fibronectin-EDA (EIIIA; EDA) is upregulated after tissue injury and may act as a "danger signal" for leukocytes to cause adverse cardiac remodeling after infarction.

Objective: In the present study, we evaluated the role of EDA in regulation of postinfarct inflammation and repair after myocardial infarction.

Restenosis after carotid surgery: the importance of clinical presentation and preoperative timing.

Background And Purpose: Carotid endarterectomy (CEA) of stable atherosclerotic plaques is associated with an increased risk for restenosis. Patients with transient ischemic attack and patients with and stroke have relatively unstable atherosclerotic plaques. However, carotid plaques stabilize over time after a cerebrovascular event due to plaque repair after rupture.

Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome.

Aims: Atherosclerotic plaque rupture and subsequent thrombus formation are the major cause of acute cardiovascular events. Local plaque markers may facilitate detection of the vulnerable plaque and help identify the patient at risk for cardiovascular events. Matrix metalloproteinases (MMPs) are prevalent in the arterial wall throughout the arterial system and are associated with local plaque destabilization.

Decreased kidney function: an unrecognized and often untreated risk factor for secondary cardiovascular events after carotid surgery.

Background And Purpose: Chronic kidney disease is an important risk factor for development and progression of atherosclerosis. The objective of the current study was to investigate the contribution of moderate kidney failure to cardiovascular (CV) mortality and morbidity after carotid endarterectomy (CEA). In addition, we investigated which proportion received optimal medical treatment or underwent diagnostic workup of the kidneys prior to CEA.

Landscape-moderated biodiversity effects of agri-environmental management: a meta-analysis.

Agri-environmental management (AEM) is heralded as being key to biodiversity conservation on farmland, yet results of these schemes have been mixed, making their general utility questionable. We test with meta-analysis whether the benefits of AEM for species richness and abundance of plants and animals are determined by the surrounding landscape context. Across all studies (109 observations for species richness and 114 observations for abundance), AEM significantly increased species richness and their abundance.

Age and coumarin-type anticoagulation are associated with the occurrence of intraplaque hemorrhage, while statins are associated less with intraplaque hemorrhage: a large histopathological study in carotid and femoral plaques.

Introduction: Intraplaque hemorrhage (IPH) is an important determinant of progression and destabilization of atherosclerotic plaque. We recently demonstrated that IPH is an independent predictor of future cardiovascular events after carotid endarterectomy. Thus far, it is unknown whether clinical patient characteristics, such as medication use, are associated with the occurrence of IPH.

Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events.

Aims: There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking.

Molecular MRI of murine atherosclerotic plaque targeting NGAL: a protein associated with unstable human plaque characteristics.

Aims: Neutrophil gelatinase-associated lipocalin (NGAL) is an effector molecule of the innate immune system. One of its actions is the prolongation of matrix metalloproteinase-9 (MMP-9) activity by the formation of a degradation-resistant NGAL/MMP-9 complex. We studied NGAL in human atherosclerotic lesions and we examined whether NGAL could act as a target for molecular imaging of atherosclerotic plaques.

Modulation of TGF-β/BMP-6 expression and increased levels of circulating smooth muscle progenitor cells in a type I diabetes mouse model.

Background: Diabetic patients experience exaggerated intimal hyperplasia after endovascular procedures. Recently it has been shown that circulating smooth muscle progenitor cells (SPC) contribute to intimal hyperplasia. We hypothesized that SPC differentiation would be increased in diabetes and focused on modulation of TGF-β/BMP-6 signaling as potential underlying mechanism.

Arteriogenesis requires toll-like receptor 2 and 4 expression in bone-marrow derived cells.

Adaptive collateral growth (arteriogenesis) is an important protective mechanism against ischemic injury in patients with cardiovascular disease. Arteriogenesis involves enlargement of pre-existent arterial anastomoses and shares many mechanistic similarities with inflammatory processes. Although infusion of the Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS) has shown to result in a significant stimulation of arteriogenesis and both Toll-like receptor 2 and 4 are involved in structural arterial adaptations, the requirement for TLRs in arteriogenesis has not yet been established.

High myeloid-related protein: 8/14 levels are related to an increased risk of cardiovascular events after carotid endarterectomy.

Background And Purpose: Myeloid-related protein (Mrp) 8/14 complex is the functional relevant form of Mrp-8 and Mrp-14. Mrp-8/14 complex is actively formed in the cytoplasm of circulating neutrophils and monocytes and then secreted. Plasma Mrp-8/14 complex is emerging as a new biomarker that may discriminate between patients with an acute coronary syndrome and those with stable coronary heart disease.

Hyaluronic acid metabolism is increased in unstable plaques.

Background: Hyaluronic acid is expressed in atherosclerotic lesions, but its exact role in atherosclerotic disease remains unknown. As degradation of hyaluronic acid by hyaluronidase into low molecular weight hyaluronic acid (LMW-HA) is associated with inflammation and Matrix Metalloproteinase (MMP)-9 activity, we hypothesized that hyaluronic acid metabolism is increased in plaques with unstable characteristics like large lipid core, high number of macrophages, MMP-9 activity, low collagen and smooth muscle cell content.

Materials And Methods: Protein was isolated from 68 carotid artery specimens.

High neutrophil numbers in human carotid atherosclerotic plaques are associated with characteristics of rupture-prone lesions.

Objective: To score the number of plaque neutrophils and relate the score to plaque morphology and inflammatory status.

Methods And Results: Neutrophils are inflammatory cells with tissue destruction capabilities that have been found at the site of an atherosclerotic plaque rupture or erosion. Poor evidence exists for neutrophil infiltration in human carotid atherosclerotic plaques, and its association with plaque morphology has not yet been described.

Histologic atherosclerotic plaque characteristics are associated with restenosis rates after endarterectomy of the common and superficial femoral arteries.

Objectives: This study assessed the predictive value of histologic plaque characteristics for the occurrence of restenosis after femoral artery endarterectomy.

Background: It would be advantageous if patients at increased risk for restenosis after arterial endarterectomy could be identified by histologic characteristics of the dissected plaque. Differences in atherosclerotic plaque composition of the carotid artery have been associated with restenosis rates after surgical endarterectomy.

Targeted deletion of the inhibitory NF-kappaB p50 subunit in bone marrow-derived cells improves collateral growth after arterial occlusion.

Aims: Adaptive collateral artery growth (arteriogenesis) is an important mechanism to maintain tissue perfusion upon arterial obstruction. Leucocytes and inflammatory mediators play a crucial role in this process. Depletion of the nuclear factor kappa B (NF-κB) p50 subunit modulates inflammatory processes in cardiovascular disease.

New predictors of adverse cardiovascular events following vascular surgery.

With the aging population and the increasing number of patients suffering from diabetes, the incidence of clinical manifestations of atherosclerotic disease is rising. Risk factors for development of atherosclerosis have been described and it is a challenge to develop risk scores that can be applied for individual patients. Specific predictors for progression of atherosclerosis and secondary manifestations of the disease are lacking.

Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease.

Innate immunity is important in the pathogenesis and progression of cardiovascular disease. Innate immune cells express various pattern-recognition receptors, among which also Toll-like receptors (TLRs). TLRs occur in atherosclerotic lesions where they are triggered by both exogenous (bacterial and viral pathogens) and endogenous (tissue damage-associated) molecules.

Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study.

Background: Identification of patients at risk for primary and secondary manifestations of atherosclerotic disease progression is based mainly on established risk factors. The atherosclerotic plaque composition is thought to be an important determinant of acute cardiovascular events, but no prospective studies have been performed. The objective of the present study was to investigate whether atherosclerotic plaque composition is associated with the occurrence of future vascular events.

Mycophenolate mofetil attenuates plaque inflammation in patients with symptomatic carotid artery stenosis.

Atherosclerosis as well as the subsequent progression towards cardiovascular events are considered to, at least partially, be a consequence of chronic inflammatory activity. Therefore, we decided to evaluate the impact of short-term immunosuppressive treatment on plaque characteristics in patients with symptomatic carotid artery stenosis. Twenty-one patients were randomized to receive either 1000 mg.

Dynamics and ecological consequences of avian influenza virus infection in greater white-fronted geese in their winter staging areas.

Recent outbreaks of highly pathogenic avian influenza (HPAI) in poultry have raised interest in the interplay between avian influenza (AI) viruses and their wild hosts. Studies linking virus ecology to host ecology are still scarce, particularly for non-duck species. Here, we link capture-resighting data of greater white-fronted geese Anser albifrons albifrons with the AI virus infection data collected during capture in The Netherlands in four consecutive winters.

Predictive risk factors for restenosis after remote superficial femoral artery endarterectomy.

Objectives: Restenosis following remote superficial femoral artery endarterectomy (RSFAE) remains a challenging problem. The determinants predicting failure are lacking. This study investigated patient characteristics with predictive value for restenosis during the first year after RSFAE.

Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine.

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives.

Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody.

Background: Reperfusion therapy for myocardial infarction is hampered by detrimental inflammatory responses partly via Toll-like receptor (TLR) activation. Targeting TLR signaling may optimize reperfusion therapy and enhance cell survival and heart function after myocardial infarction. Here, we evaluated the role of TLR2 as a therapeutic target using a novel monoclonal anti-TLR2 antibody.