The Complexity of Arterial Classical Monocyte Recruitment

Accumulation of classical monocytes is imperative for the progression ofatherosclerosis. Hence, therapeutic interference with mechanisms oflesional monocyte recruitment, the primary mechanism controllingmacrophage accumulation, may allow for targeting atheroprogression andits clinical complications. Here, we review the important role ofclassical monocytes in atheroprogression as well as their routes ofarterial recruitment. We specifically highlight the role of celladhesion molecules as well as of platelet-derived chemokines andneutrophil-borne alarmins

(Re) Solving Repair After Myocardial Infarction

Cardiovascular diseases, including myocardial infarction and its complications such as heart failure, are the leading cause of death worldwide. To date, basic and translational research becomes necessary to unravel the mechanisms of cardiac repair post-myocardial infarction. The local inflammatory tissue response after acute myocardial infarction determines the subsequent healing process. The diversity of leukocytes such as neutrophils, macrophages and lymphocytes contribute to the clearance of dead cells while activating reparative pathways necessary for myocardial healing. Cardiomyocyte death triggers wall thinning, ventricular dilatation, and fibrosis that can cause left ventricular dysfunction and heart failure. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction to prevent cardiac death. Current therapies for heart failure after myocardial infarction are limited and non-curative. At the moment in clinic, conventional surgical interventions such as coronary artery bypass graft or percutaneous coronary interventions are only able to partially restore heart function, with a minor improvement in the left ventricular ejection fraction. The goal of this review is to provide an overview of endogenous myocardial repair mechanisms possibly transferable to future treatment strategies. Among the innovative factors identified as essential in cardiac healing, we highlight specialized pro-resolving mediators as the emerging factors that provide the key molecular signals for the activation of the reparative cells in the myocardium

Resolution of inflammation: an integrated view

O.S. is supported by the NWO (VIDI project 91712303), theDFG (SO876/3-1, SO876/6-1, FOR809, SFB914 TPB08), theGerman-Israeli Foundation, and the Else Kro¨ner FreseniusStiftung. M.P. is supported by the Wellcome Trust (program086867/Z/08), the Arthritis Research UK, the British HeartFoundation (PG/09/060 and PG/11/48/28981) and the MedicalResearch Council

Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis

Neutrophil extracellular traps expelled from suicidal neutrophils comprise a complex structure of nuclear chromatin and proteins of nuclear, granular, and cytosolic origin. These net-like structures have also been detected in atherosclerotic lesions and arterial thrombi in humans and mice. Functionally, neutrophil extracellular traps have been shown to induce activation of endothelial cells, antigen-presenting cells, and platelets, resulting in a proinflammatory immune response. Overall, this suggests that they are not only present in plaques and thrombi but also they may play a causative role in triggering atherosclerotic plaque formation and arterial thrombosis. This review will focus on current findings of the involvement of neutrophil extracellular traps in atherogenesis and atherothrombosis

Organ-Specific Mechanisms of Transendothelial Neutrophil Migration in the Lung, Liver, Kidney, and Aorta

Immune responses are dependent on the recruitment of leukocytes to the site of inflammation. The classical leukocyte recruitment cascade, consisting of capture, rolling, arrest, adhesion, crawling, and transendothelial migration, is thoroughly studied but mostly in model systems, such as the cremasteric microcirculation. This cascade paradigm, which is widely accepted, might be applicable to many tissues, however recruitment mechanisms might substantially vary in different organs. Over the last decade, several studies shed light on organ-specific mechanisms of leukocyte recruitment. An improved awareness of this matter opens new therapeutic windows and allows targeting inflammation in a tissue-specific manner. The aim of this review is to summarize the current understanding of the leukocyte recruitment in general and how this varies in different organs. In particular we focus on neutrophils, as these are the first circulating leukocytes to reach the site of inflammation. Specifically, the recruitment mechanism in large arteries, as well as vessels in the lungs, liver, and kidney will be addressed

Manipulation of Optimal Matchings via Predonation of Endowment

In this paper we answer a question posed by Sertel and Sanver (2002) on the manipulability of optimal matching rules in matching problems with endowments. We characterize the classes of consumption rules under which optimal matching rules can be manipulated via predonation of endowment.G. Fiestras-Janeiro received financial support from the Spanish Ministerio de Ciencia y Tecnología and the FEDER through projects PB98-0613-C02-02 and BEC2002-04102-C02-02, and from the Xunta de Galicia through grant PGIDT00PXI20703PN. The work of F. Klijn is partially supported by Research Grant BEC2002-02130 from the Spanish Ministerio de Ciencia y Tecnología and by a Marie Curie Fellowship of the European Community programme “Improving Human Research Potential and the Socioeconomic Knowledge Base” under contract number HPMF-CT-2001-01232. The work of E. Sánchez is supported by project BEC2002-04102-C02-02 from the Spanish Ministerio de Ciencia y Tecnología and the FEDER

The Complexity of Arterial Classical Monocyte Recruitment

Accumulation of classical monocytes is imperative for the progression ofatherosclerosis. Hence, therapeutic interference with mechanisms oflesional monocyte recruitment, the primary mechanism controllingmacrophage accumulation, may allow for targeting atheroprogression andits clinical complications. Here, we review the important role ofclassical monocytes in atheroprogression as well as their routes ofarterial recruitment. We specifically highlight the role of celladhesion molecules as well as of platelet-derived chemokines andneutrophil-borne alarmins

(Re) Solving Repair After Myocardial Infarction

Cardiovascular diseases, including myocardial infarction and its complications such as heart failure, are the leading cause of death worldwide. To date, basic and translational research becomes necessary to unravel the mechanisms of cardiac repair post-myocardial infarction. The local inflammatory tissue response after acute myocardial infarction determines the subsequent healing process. The diversity of leukocytes such as neutrophils, macrophages and lymphocytes contribute to the clearance of dead cells while activating reparative pathways necessary for myocardial healing. Cardiomyocyte death triggers wall thinning, ventricular dilatation, and fibrosis that can cause left ventricular dysfunction and heart failure. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction to prevent cardiac death. Current therapies for heart failure after myocardial infarction are limited and non-curative. At the moment in clinic, conventional surgical interventions such as coronary artery bypass graft or percutaneous coronary interventions are only able to partially restore heart function, with a minor improvement in the left ventricular ejection fraction. The goal of this review is to provide an overview of endogenous myocardial repair mechanisms possibly transferable to future treatment strategies. Among the innovative factors identified as essential in cardiac healing, we highlight specialized proresolving mediators as the emerging factors that provide the key molecular signals for the activation of the reparative cells in the myocardium