Three Facets of Intussusceptive Angiogenesis

The term intussusceptive angiogenesis circumscribes a host of processes that are involved in generation, growth, and final remodeling of vascular entities with diverse morphological and functional outcomes. Although chronologically sequential, the processes overlap both in space and time, affecting different components of the vascular bed.

Intussusceptive Microvascular Growth: Expansion of Capillary Plexuses

Intussusceptive microvascular growth (IMG) represents a widespread phenomenon, by which capillary plexuses expand by simultaneous scattered pillar formation and successive pillar enlargement. By these means, new micro-vascular segments arise without dramatic changes in the dimensions and functional characteristics of their components (Figure 2). IMG favors the rapid expansion of the primitive capillary plexuses, thus providing a large surface area for the exchange of oxygen, carbon dioxide, and nutrients. As mentioned previously, IMG was first observed in the growing postnatal lung [1] and then in the microvascu-lature of many other tissues and organs, both in normal and pathological microvascular growth, such as retina, kidney, CAM, liver, intestines, stomach, excretory glands, spleen, skeletal muscle, heart, brain, in a model of tissue repair, during the cyclic vascular changes in the endometrium, in cerebral vascularization after stroke, and during tumor angiogenesis. Intussusception is a widespread, practically ubiquitous phenomenon that occurs in the vascular systems

Figure 2 Drawing representing the process of intussusceptive microvascular growth (IMG). The capillary plexus expands from its initial stage in (a) to status (b) by insertion of new pillars (arrows) and by enlargement of already existing ones (arrowheads).

of all species thus far investigated, including rat, mice, rabbit, chick, fish, and human. Actually, in many older reports dealing with different angiogenic aspects, it is possible to recognize the well-documented signs of intussusception; they were, however, not recognized as a mechanism of angiogenesis. It is now evident that IMG represents a general and ubiquitous mechanism of capillary growth, by which the capillary beds of organs, which arise initially by sprouting and/or vasculogenesis, can undergo rapid expansion without any compromise in vascular physiology or function thanks to low vascular permeability and a low rate of endothelial cell proliferation [3, 6, 8, 9].

Intussusceptive Arborization: Formation of a Feeding Vascular Tree

Intussusceptive arborization (IAR) represents a mechanism whereby preferentially perfused segments of a capillary plexus can be transformed into terminal arterioles or collecting venules, patterning in this way a hierarchic vascular tree. IAR is initiated by the formation in the capillary bed of double rows of lined-up "vertical" tissue pillars, which demarcate future feeding vessels. These pillars undergo reshaping into narrow tissue septa that progres sively fuse to delineate a new vascular entity. The remaining connecting bridges are "severed" by the formation of "horizontal" folds, the feeding vessels being thereby definitively separated from the capillary plexus. As a result of this process, a complex arterial and venous vascular tree arises to form a second layer of draining and feeding vessels (Figure 3).

IAR provides the vasculature with an important angio-adaptive mechanism. Any capillary plexus expansion is associated with an increase in the mean capillary path length between arteries and veins, with deleterious consequences for gas and nutrient exchange. The formation of new terminal supplying and draining branches is necessary, and this is achieved via IAR. The IAR process could be observed in all investigated organs and systems, but for easy demonstration it is mostly shown in nearly two-dimensional capillary beds, such as the chloroid of the eye and the chicken CAM. In these models, the de novo segregated arterial and venous

Figure 3 Drawing representing the process of intussusceptive arborization (IAR). Within a capillary plexus, a series of "vertical" pillars arise (arrows in a), demarcating the pathway of future feeding vessels. These pillars undergo reshaping and fusion to form narrow tissue septa (arrows in b). "Horizontal" pillars and folds are then formed (arrowheads in c), which separate the feeding vessels from the capillary plexus (d). Adapted from Djonov et al. 2000 [5], with the authors' and publisher's permission.

Figure 3 Drawing representing the process of intussusceptive arborization (IAR). Within a capillary plexus, a series of "vertical" pillars arise (arrows in a), demarcating the pathway of future feeding vessels. These pillars undergo reshaping and fusion to form narrow tissue septa (arrows in b). "Horizontal" pillars and folds are then formed (arrowheads in c), which separate the feeding vessels from the capillary plexus (d). Adapted from Djonov et al. 2000 [5], with the authors' and publisher's permission.

vascular trees form an easily detectable second layer atop the capillary plexus [3-5, 8-9].

Intussusceptive Branching Remodeling: Optimization of Branching Geometry and Vascular Pruning

Intussusceptive branching remodeling (IBR) refers to the process by which the branching geometry of supplying vessels is modified, thereby optimizing the pre- and post-capillary flow properties. IBR can also lead to the removal of putative supernumerary branches (vascular pruning), thereby optimizing the efficiency of the blood supply and the hierarchy of the vascular tree. Implementation of IBR is accomplished via transluminal pillars and folds, which are inserted close to the bifurcation sites of arteries and veins of up to 120 mm in diameter. These structures appear de novo and are capable of rapidly changing the vascular geometry and the hemodynamic properties at the affected branching points.

The pillars located close to bifurcation points enlarge (alternately elongate into flat longitudinal folds) until they merge with connective tissue in the branching angle (Figure 4). Thus, IBR narrows the branching angle by relocating the branching point more proximally. This may represent an important adaptive response to the continually increasing blood flow and blood pressure during embryogenesis and growth. Second, IBR optimizes the hemodynamic conditions at bifurcation sites by remodeling the diameter of one or both branches (mainly by "pillar augmentation"). Consequently, IBR yields a branching pattern that approximates the ideal hemodynamic condition predicted by Murray's Law of minimal power consumption and constant shear stress. Third, IBR is implemented in the process of vascular pruning by the successive asymmetric formation of pillars. The subtotal lumen obstruction of one of the daughter branches followed by reduction in blood flow probably contributes to the regression, retraction, and ultimate atrophy of the affected branch (Figure 4) [7-9].

From the mechanisms of IAR and IBR, detected more recently, it appears that the intussusceptive angiogenic principle represents an important morphogenetic machinery affecting all components of vascular beds: as the expansion of capillary beds (IMG), the segregation of small arteries and veins (IAR), and finally the optimization of the branching geometry and vascular pruning by IBR.

Was this article helpful?

0 0
Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

Get My Free Ebook


Post a comment