Vascular remodelling processes: Cells, signals and their integration

Abstract

Thromb Haemost 2007; 98: 919–921 The vasculature is one of the most important and complex organs in the mammalian body and the first functional organ to be formed during embryonic development. The initial vascular plexus consists of a homogenous web of endothelial cell tubes and sacs, which later become remodelled into a mature network. Remodelling involves the creation of large and small vessels, the establishment of directional flow, the association with mural cells (pericytes and smooth muscle cells) and the adjustment of vascular density which is essential for the transportation of oxygen and nutrients to and the removal of waste products from the tissues. The maintenance of vessel integrity and the control of vessel physiology and haemodynamics during embryonic development has functional consequences on postnatal and adult life (1). In general vascular remodelling processes are characterized by structural changes of the vessel wall involving a variety of cellular activities such as proliferation, migration, apoptosis, or restructuring of the extracellular matrix. Together with intercellular activities this may lead to recruitment of stem and progenitor cells, interaction of blood cells with the vascular wall, rearrangement of vascular wall cell topography, resulting in modulation of vascular barrier function and vascular growth into new or existing tissues. Vascular remodelling processes have been recognized in particular to play a role in a variety of disease states, including atherosclerosis, ischemic diseases, systemic and pulmonary hypertension, tumor growth, metabolic syndrome, diabetes mellitus or renal pathologies (2). In this Theme Issue of Thrombosis and Haemostasis, which comprises the second part of a series of review articles and original manuscripts which are based on scientific contributions presented at the Annual Meeting of the Society of Microcirculation and Vascular Biology at the German Heart Center atTU in Munich, October 12-14, 2006, important new findings are highlighted which are related to different aspects of vascular remodelling processes. It was not until 10 years ago that the importance of endothelial progenitor cells (EPC) for the formation of new blood vessels was appreciated. More recently, progenitor cells have been found in many (adult) organs and have been implicated to contribute to physiological and pathophysiological regenerative processes. In their review, Stellos and Gawaz (3) summarize current findings regarding the recruitment, survival and differentiation of EPC with a specific focus on the role of platelets in these events. Indeed, in addition to their function in haemostasis and thrombus formation, platelets appear to be involved in vascular or tissue regeneration, since at their site of destination they release various growth factors, chemokines and cellular aganists. Platelets are capable of interacting with the vascular wall or with other circulating blood cells including EPC, thereby contributing to their recruitment as well as to their differentiation into mature endothelial cells, macrophages or even foam cells. However, current anti-platelet therapy does not seem to be effective in preventing EPC recruitment and differentiation. Thus, additional insights are required into the nature of specific (non-platelet) mediators which would allow selective recruitment of bone marrow-derived stem and progenitor cells to specific organs, with respective consequences for organ vascularization and regeneration. In addition to circulating EPC, also vascular wall-resident EPC (VW-EPC) have been identified. Ergun et al. (4) describe the potential role of VW-EPC compared to circulating or bone marrow-derived EPC for new vessel formation in association with different diseases. VW-EPC have been found in large and middlesized human arteries and veins in several organs in the so called “vasculogenic zone” which is located between smooth muscle cell and adventitial layers.The authors conclude that the incorporation of pre-existing vessels (e.g. promoted a tumor) could initially lead to the mobilization and recruitment of local VW-EPC as well as tissue-resident EPC for new vessel formation followed by activation of mature endothelial cells and circulating EPC. Similar processes are discussed for VW-ECP in situations of inflammation, ischemia or atherosclerosis, since VW-EPC have the intriguing ability to migrate through the smooth muscle cell layer towards the vascular lumen. Although the exact role of VW-EPC in © 2007 Schattauer GmbH, Stuttgart