Structural adaptation of normal and tumour vascular networks

Abstract

Vascular networks are dynamic structures, adapting to changing conditions by structural remodelling of vessel diameters and by growth of new vessels and regression of existing vessels. The vast number of blood vessels in the circulatory system, more than 10 9, implies that vessels' arrangement and structure are not under individual genetic control but emerge as a result of generic responses of each segment to the various stimuli that it experiences. To obtain insight into the types of response that are needed, a network-oriented approach has been used, in which theoretical models are used to simulate structural adaptation in vascular networks, and the results are compared with experimental observations. With regard to the structural control of vessel diameters, this approach shows that responses to both haemodynamic and metabolic stimuli are needed for the formation of functionally adequate and efficient network structures. Furthermore, information transfer in both upstream and downstream directions is essential for balancing flows between long and short flow pathways. Otherwise, functional shunting occurs, that is, short pathways become enlarged and flow bypasses longer pathways. Information transfer in the upstream direction is achieved by conducted responses communicated along vessel walls. Simulations of structural adaptation in tumour microvascular networks indicate that impaired vascular communication, resulting in functional shunting, may be an important factor causing the dysfunctional microcirculation and local hypoxia typically observed in tumours. Anti-angiogenic treatment of tumours may restore vascular communication and thereby improve or normalize flow distribution in tumour vasculature. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.