Angiogenesis Revisited: Cell Biology and Biophysics During Real and Simulated Blood Vessel Morphogenesis

Haymo Kurz

Institute of Anatomy, University of Freiburg, 79104 Freiburg, Germany

Understanding how blood vessels are made, or how they can be prevented from being made, i.e., angiogenesis research, has been identified as a major issue in developmental and tumor biology. Successfully manipulating angiogenesis has also become key for future engineering of vascularized tissues and organs. Hence, mechanisms involved in the generation, maintenance and remodeling of blood vessels need to be studied, both experimentally and by means of computer simulations. By doing so, we may also hope with respect to regeneration to better define conditions that will lead to optimally adapted vascular networks with tissue-specific transport properties. Two approaches will be introduced as examples on how real world experiments and computer simulations may jointly enhance our understanding of angiogenesis. First, recent findings on non-sprouting modes of angiogenesis, so-called intussusceptive growth (IMG), arborization (IAR), and bifurcation remodeling (IBR) will be presented. IMG is the typical way of making new capillaries in respiratory organs, but may also contribute significantly in other vascular beds to enlargment of capillary plexuses. IAR produces pre- and postcapillary vessels from a capillary plexus, whereas IBR does not generate new vessel segments, but may be involved in functional optimization of bifurcation geometry, displacement of bifurcation sites, or removal of branches at bifurcations. Common to all three modes of intussusception is the formation of transluminal pillars or folds in perfused vessels through interactions of endothelial and mural cells. Functional and morphological analysis has provided evidence that hemodynamic forces may be important for intussusception and for bifurcation optimization to occur [1,2]. Second, computer simulations will be presented that were inspired by intussuceptive angiogenesis. Geometrical and physiological properties, vessel growth and regression, hemodynamic and chemical influences were implemented and led to networks closely mimicking vascular beds. Interestingly, typical interdigitations of arteries and veins were achieved by using shear stress for controlling angiogenesis. Predictions of network morphology, hemodynamics and transport properties were in agreement with experimental data [3,4].

References
[1] Djonov V, Kurz H, Burri PH. Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism. Dev Dynam 2002; 224:391-402.
[2] Kurz H, Burri PH, Djonov VG. Angiogenesis and vascular remodeling by intussusception - from form to function. News Physiol Sci 2003; 18: 65-70.
[3] Kurz H, Sandau K. Modelling of blood vessel development - bifurcation pattern and hemodynamics, optimality and allometry. Comments Theor Biol 1997; 4/4: 261-291.
[4] Gödde R, Kurz H. Structural and biophysical simulation of angiogenesis and vascular remodeling. Dev Dynam 2001; 220: 387-401.

Acknowledgment:
The contributions of PH Burri and VG Djonov (Bern), K Sandau (Darmstadt), R Gödde and W Düchting (Siegen) are gratefully acknowledged.