15/05/2013: Vascular Networks: Structure, Function and Design Principles, Axel R. Pries


Vascular Networks: Structure, Function and Design Principles


May 15, 2013, 16:15, ML H 44, ETH Zurich

Prof. Axel R. Pries
Department of Physiology and CCR, ChariteĢ and Deutsches Herzzentrum

 
Microvascular networks are highly dynamical and heterogeneous structures which have to provide low diffusion distances from capillaries to all tissue cells as well as efficient convective distribution of blood flow through larger vessels. Central to the development of adequate vascular networks is the combination of stochastic processes of angiogenesis with refining processes of vascular diameter adaptation and pruning. This combination allows generation and dynamic adaptation of vascular beds efficiently and with acceptable heterogeneity in levels of local supply.
Signals derived from vascular function including blood flow (shear stress), blood pressure (circumferential wall stress) and tissue metabolic state govern the structural adaptation of vascular beds with respect to vessel number, diameter, wall thickness and length in response to functional requirements. In this process of angioadaptation, the properties of peripheral vascular beds are determined by the interplay between vascular and cellular reactions to signals related to functional stimuli and the functional implications of these reactions.
Many components and mechanisms of angioadaptation have been described. However, the complex interaction of functional stimuli, molecular mediators, cellular reactions and resulting functional properties of vascular beds is still poorly understood. Integrative approaches, including the analysis and extrapolation of experimental findings by mathematical models have been presented which provide prediction of realistic vascular properties based on a generic set of adaptation characteristics. These models allow quantitative analysis of the relation between vascular reaction patterns to mechanical stimuli and properties of terminal vascular beds including situations with aberrant adaptive properties or systemic conditions.
Despite the regulating effects of vascular adaptation, topological (branching pattern), structural (e.g. diameter or length) and functional (e.g. shear stress or tone) parameters exhibit systematic correlations and marked heterogeneity. Heterogeneity is also an inevitable property of microvascular networks due to geometric constraints and principles of vascular pattern generation (‘pro-heterogenic effects’). Thus, heterogeneity has to be addressed to understand and model the function of microvascular beds. Within this framework, the concept of ‘optimal values’ may be replaced by that of ‘acceptable heterogeneity,’ and observed heterogeneity reflects the balance between pro-heterogenic effects and biological control mechanisms, including information transfer from capillaries to feeding and draining vessels. Compromised ability for network refinement by angioadaptation is probably involved in a number of pathologies characterized by excessive heterogeneity, including tumor vascularization, sepsis and aging.
 
Host: Prof. P. Jenny