This book is a compilation of the lectures and oral and poster communications presented at the Advanced Study. Institute on "Vascular Endothelium: Physiological Basis of Clinical Problems II," which took place between June 20 and 30, 1992 in Rhodes, Greece. This third in a series of ASIs on vascular endothelium continued on the theme of the first (1988) ASI on "Receptors and Transduction Mechanisms" and particularly expanded that of the 1990 conference on ''Physiological Basis of Clinical Problems. " We continued the successful practice of bringing together clinicians and scientists: this was reflected equally well in the composition of the organizing committee as in the background of the particiJ?ants. Endothelial cell functions and dysfunctions present as many challenges to the mvestigator as they do to the curious clinical practitioner. As these problems are necessarily different, this unique ten-day co-habitation of these individuals continued to offer fresh outlooks to each, stimulated potential collaborative efforts and, most importantly, advanced --ever so slightly--our knowledge of vascular biology. This year's conference was further enriched by the presence of several of our colleagues from Eastern Europe whom we are delighted to welcome as officially sponsored participants to this and future NATO-supported meetings. It is never superfluous to remind readers and participants that those signing at the bottom of this page, while responsible for many of the ASI's and the book's deficiencies, are but three of the many contributors to the successes.

Proceedings of a NATO ARW held in Crete, Greece, June 22-July 1, 1996

This monograph contains the proceedings from the Advanced Study Institute on "Vascular Endothelium: Physiological Basis of Clinical Problems" which took place in Corfu, Greece in June 1990. The meeting consisted of twenty-eight lectures, most of them adapted as full length papers in this volume, as well as numerous short oral and poster communications which are abstracted and also included in alphabetical order (pages 239-302). There were ninety-six participants from ten NATO and four other European countries. The meeting was the second in as many years dealing with a specific subject in Endothelial Cell biology. Following the 1988 discussion on "Receptors and Transduction Mechanisms", the present ASI recognized and tried to deal with the increasing overlap in interest between basic scientists studying endothelial cell functions and clinicians facing problems of known or suspected endothelial pathological involvement. As with any similar effort, we opted to be selective, rather than fail by trying to be inclusive, in the subjects covered. We chose to discuss diseases, such as atherosclerosis, sepsis, ARDS and stroke, based on their relevance to endothelial cell function and urgent need for new insights into their pathogenesis and treatment. Similarly, we examined endothelial cell functions by considering their relevance to disease and their potential for elucidating important pathologies. Obviously, some areas were covered superficially or not at all; this should not distract from their importance, but rather reflect on the constraints of time and -not at all negligibly -the bias of the organizing committee.

This monograph contains the contributions to the NATO Advanced Studies Institute on "Vascular Endothelium: Responses to Injury", which took place in Crete, Greece from June 18 to 27, 1994. This was the fourth in the series of NATO-supported ASIs in selected specific areas of endothelial cell biology, which began in 1988. Each time, it has combined clinical with basic scientists and renowned experts with novices in the field, in an attractive setting conducive to dissemination of knowledge, high quality discussions and exchange of ideas. This, as well as previous ASIs, reflects the hard work of numerous people. As Co- Directors, we have been particularly fortunate to benefit from the expert advice of the Organizing Committee, which included Elizabetta Dejana, Alberto Mantovani and Magdi Yacoub. Their insightful suggestions helped formulate the scientific program of the ASI. We are also grateful for the work and dedication of the local organizing committee of Thomie Douraki, Stylianos Orfanos, Panayotis Behrakis, Michael Maragoudakis and Lydia Argyropoulos who tirelessly looked after the main details necessary to ensure that all of us enjoyed the meeting. Similarly, we wish to thank Jim Parkerson, Connie Snead, Andreas Papapetropoulos and Nandor Marczin for their assistance in various aspects of the many preparations for the conference. A very special thanks goes to Annie Cruz, the ASI Co- ordinator, for her efficient, solicitous and pleasant demeanor during the months prior to the ASI and especially during the ten days of the conference.

Proceedings of a NATO ARW held in Crete, Greece, June 22-July 1, 1996

This volume explores the various molecular pathways via which endothelial cells communicate among them as well as with other vascular cells (e.g., smooth muscle cells, leukocytes, platelets, fibroblasts, etc.) in order to transduce physiologic and pathologic signals. The most important pathologies discussed are: - pulmonary vascular diseases - thrombosis - hypertension (systemic and pulmonary) - inflammation - angiogenesis - cerebrovascular disease - transplantation - atherosclerosis. The largest fraction of time was devoted to the mechanisms and signals underlying these diseases.

Free Radicals/Ischemia Reperfusion Injury: Basal Relief of EDRF under Conditions of Oxidant Stress; N. Marczin, et al. Invasion and Neoplasia: Interaction of Malaria-Infected Cells with the Vascular Wall; G. Senaldi, et al. EndothelialTumor Cell Interactions In vitro and In vivo; R. Giavazzi, et al. Altered Vascular Reactivity: Altered Vascular Reactivity in Coronary Artery Disease; J. Zanzinger, E. Bassenge. Isoforms of Nitric Oxide Synthase and the Nitric Oxide-Cycle GMP Signal Transduction System; F. Murad, et al. Inflamation/Atherosclerosis: Proinflammatory Role of Leukocyte Adhesion Molecules; J.M. Harlan, et al. Circulating Endothelial Adhesion Molecules; J.L. Gordon, et al. Organ Transplantation/Rejection: Experimental Cell Transplantation and Gene Therapy Techniques in the Treatment of Liver Disease; A.A. Demetriou, et al. 6 additional articles. Index.

I. Clinical Topics.- The Clinical Profile of Sepsis and the Adult Respiratory Distress Syndrome.- The Participation of the Complement System in Atherosclerotic Vascular Disease.- The Spectrum of Atherosclerosis in the Human.- Cerebral Endothelial Injury in Stroke, Brain Trauma and Hypertension.- II. General Concepts in Endothelial Cell Pathophysiology.- Free-Radical Mediated Actions on Endothelial Cells of the Intact Lung.- Regulation of Vascular Function by Vascular Permeability Factor.- III. Chemical Mediators of Endothelial Cell Injury.- Endothelial Cells as Targets for and Producers of Cytokines.- Roles of Vascular Cells in Inflammation and Immunopathology.- The Biochemistry, Cell and Molecular Biology of Type 1 Plasminogen Activator Inhibitor.- IV. Endothelial Cell Interaction with Blood Components.- Purine Regulation of Endothelial Cells: Relevance to Pathophysiology.- Autoantibodies to Endothelial Cells.- Leukocyte-Endothelial Cell Interactions.- V. Vascular Responses to Endothelial Cell Injury.- Endothelial Function in Human Coronary Bypass Grafts.- Altered Renovascular Endothelial Functions During Nephrotoxicity.- Cerebral Endothelial Function: Physiology and Pathophysiology.- Mechanisms of Altered Reactivity in the Cerebral Microcirculation.- VI. Mechanisms of Endothelial Cell Dysfunction.- The Role of Apolipoprotein E and Apolipoprotein B in Atherosclerosis.- Endothelial Cell-Matrix Interactions in Health and Disease.- Biosynthesis and Assembly of von Willebrand Factor by Vascular Endothelial Cells: Relevance to Pathophysiology.- VII. Markers of Endothelial Cell Injury and Repair.- Monitoring of Endothelial Plasmalemmal Ectoenzyme Function as an Index of Endothelial Injury and Repair.- Pathophysiological Significance of Endothelial Cell Integrins.- VIII. Epilogue.- Vascular Endothelium: Physiological Basis of Clinical Problems.- IX. Abstracts of Oral and Poster Presentations.- X. List of Participants.- XI. Index.