The F11 receptor (F11R/JAM-A) in atherothrombosis: overexpression of F11R in atherosclerotic plaques

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A - antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our in-vitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.     

Recollections of Professor Henry Barcroft, F.R.S.

Professor Henry Barcroft, MD, FRS, Emeritus Professor of Physiology in St. Thomas' Hospital Medical School in London died on 11 January 1998, aged 93. He was born in Cambridge on 18 October 1904 where his father, Joseph Barcroft, a famous physiologist, worked with Foster and Langley and subsequently was appointed to the Chair of Physiology. Henry Barcroft followed in his father's footsteps. During his career as Professor of Physiology firstly at The Queen's University of Belfast and subsequently at St. Thomas's Hospital London, he made significant studies on the nervous and humaral control of human blood vessels. His success as a research scientist stemmed partly from his ability to simplify complex phenomena in a way that permitted them to be broken into component parts and tested and partly from his technical ingenuity that permitted simple, inexpensive measurements of difficult physiological variables. Perhaps the most important factor, however, was his ability to bring out and stimulate aptitudes and enthusiasms in others. Completely unselfish himself, he gave individuals every opportunity to develop their talents, and so make themselves known to a wide circle of interested medical scientists. In many ways, his life was a guidebook for young scientists on how to make the most of their opportunities.