Recent advances in vascular biology: Selected highlights from IVBM 2008

Abstract

Thromb Haemost 2009; 101: 997–998 The contributions encapsulated in this themed issue of Thrombosis and Haemostasis derive from invited lectures at the 15th International Vascular Biology Meeting (IVBM) held in June, 2008 in Sydney, Australia. IVBMs, which are held every two years, have become the most prestigious international biomedical conference in blood vessel biology and disease. The scientific programme featured 130 talks couched in seven plenary sessions (14 keynote speakers), 17 workshops (2–3 invited speakers and 2–3 speakers selected from abstracts), two sponsored symposia, and almost 400 posters. The programme also featured three memorial orations honoring true giants in vascular biology that had passed away since the last IVBM in Amsterdam in 2006, namely Judah Folkman, Tucker Collins and Rudi Busse. The following provides a brief synopsis of six areas covered at IVBM 2008. Angiogenesis underpins normal physiological processes such as reproduction and wound healing, as well as a wide range of vascular disorders such as atherogenesis, and invasive tumour growth and metastasis. Angiogenesis involves the suppression of adhesion receptors, such as ICAM-1, VCAM-1, E-selectin and CD34 in tumour endothelium (1). Angiogenesis inhibitors are able to normalise endothelial adhesion molecule expression in tumour blood vessels, restoring leukocyte vessel wall interactions and enhancing inflammatory infiltration in the tumours, thus making tumours more vulnerable to attack by the immune system. Arjan Griffioen (VU University Medical Center, Amsterdam, The Netherlands) and Florry Vyth-Dreese (Netherlands Cancer Institute, Amsterdam, The Netherlands) have reviewed (2) the potential of angiostasis therapy to stimulate immune-mediated tumour inhibitory activity and speculate on new therapeutic approaches involving angiostasis in immunotherapy. The various mechanisms with which angiogenesis inhibitors might improve immuno-targeted approaches include tumour cell lysis stimulating tumour antigen presentation, reduced inhibitory molecule load that improves immune reactivity, limited release of immunosuppressive cytokines into the tumour microenvironment, and the creation of a pro-inflammatory microenvironment. Blood vessels adjust their calibre size in order to adapt to the demands of tissues or organs for nutrients and oxygen. The mechanisms involved in calibre size determination in blood vessels are not well understood. Nobuyuki Takakura and Hiroyasu Kidoya (Osaka University, Osaka, Japan) recently discovered that apelin, a factor secreted from endothelial cells following activation of Tie2 receptor tyrosine kinase, regulates the calibre size of blood vessels through its cognate endothelial G proteincoupled receptor APJ (3). Takakura and Kidoya have reviewed (4) the cooperative effect of apelin and VEGF on endothelial cell proliferation and capillary tube formation, and apelin’s regulation of cell-to-cell aggregation and cord hollowing. Integrins are heterodimeric cell-surface molecules that mediate molecular interactions between cells and their extracellular matrix (ECM) environment (5). These signalling receptors transmit information in both “inside-out” and “outside-in” directions across the cell membrane. A necessary and sufficient final step in integrin activation is the binding of the cytoskeletal protein talin to the integrin β-subunit. Brian Petrich (University of California, San Diego, USA) has reviewed (6) our current understanding of the mechanisms regulating the interaction of talin and that of numerous other proteins (such as filamin and kindlin) with the β-integrin subunit and modulation of integrin activation. Our growing appreciation of the functional significance of integrin signalling in haemostasis and thrombosis has been facilitated by mutational analysis in recombinant cell lines and very recently by the use of genetically modified mice. These and other advances focusing mainly on integrin αIIbβ3 (GPIIb-IIIa) are reviewed. Antibodies represent the fastest growing class of human therapeutics and the second largest class of drugs after vaccines, and these molecules are widely used as therapeutic agents in a diverse range of clinical settings, including cancer, inflammatory disease and cardiovascular disease. Single-chain antibodies (7) are one of the smallest possible formats for a recombinant antibody. Karlheinz Peter and colleagues (Baker IDI Heart and Diabetes Institute, Melbourne, Australia) have described (8) the © 2009 Schattauer GmbH, Stuttgart