Vessel Arterial-Venous Plasticity in Adult Neovascularization

Abstract

ObjectiveProper arterial and venous specification is a hallmark of functional vascular networks. While arterial-venous identity is genetically pre-determined during embryo development, it is unknown whether an analogous pre-specification occurs in adult neovascularization. Our goal is to determine whether vessel arterial-venous specification in adult neovascularization is pre-determined by the identity of the originating vessels.Methods and ResultsWe assessed identity specification during neovascularization by implanting isolated microvessels of arterial identity from both mice and rats and assessing the identity outcomes of the resulting, newly formed vasculature. These microvessels of arterial identity spontaneously formed a stereotypical, perfused microcirculation comprised of the full complement of microvessel types intrinsic to a mature microvasculature. Changes in microvessel identity occurred during sprouting angiogenesis, with neovessels displaying an ambiguous arterial-venous phenotype associated with reduced EphrinB2 phosphorylation.ConclusionsOur findings indicate that microvessel arterial-venous identity in adult neovascularization is not necessarily pre-determined and that adult microvessels display a considerable level of phenotypic plasticity during neovascularization. In addition, we show that vessels of arterial identity also hold the potential to undergo sprouting angiogenesis.

Vascularization strategies of engineered tissues and their application in cardiac regeneration

“…In addition, after in vivo implantation, MF-based constructs were able to generate vessels with specific arterio-venous phenotypes, as characterised by the presence of either EphrinB2 or EphB4 positive vessels (arterial and venous identity, respectively) (Fig. 2C) [62]. Analysis of vessel arterio-venous plasticity using MFs obtained from transgenic reporter mice and a magnetic bead isolated method to harvest MFs of arterial identity revealed that arterial-venous identity in adult neovascularization is not necessarily pre-determined and that adult microvessels display a considerable level of phenotypic plasticity during neovascularization, with microvessels of arterial identity being able to give rise to full neovasculature containing both arterial and venous microvessels [62].…”

“…2C) [62]. Analysis of vessel arterio-venous plasticity using MFs obtained from transgenic reporter mice and a magnetic bead isolated method to harvest MFs of arterial identity revealed that arterial-venous identity in adult neovascularization is not necessarily pre-determined and that adult microvessels display a considerable level of phenotypic plasticity during neovascularization, with microvessels of arterial identity being able to give rise to full neovasculature containing both arterial and venous microvessels [62]. These MF-based constructs have been shown to display blood perfusion in vivo as early as 2 days post implantation [61].…”

“…Scale bar, 100 mm. (Reproduced from [62]). D. Representative images of vasculatures formed 14 and 28 days postimplantation of freshly isolated and cultured SVFs (fSVF and cSVF) from GFP rats with MF derived form non-GFP rats into immunocompromised mice.…”

Making Microvascular Networks Work: Angiogenesis, Remodeling, and Pruning

“…Vessels that were initially capillaries can turn into larger conductance vessels (and vice versa) at any location within the developing network. Redistribution of flow directions can cause transitions from venous to arterial vessel type in response to the resulting hemodynamic and metabolic conditions (22,53), and flow conditions can thus determine vascular identity (17,43).…”

Biofabrication of Vascular Networks

“…While hemodynamics most certainly are critical in establishing mature, stable vessel and network phenotypes, there is possibly some genetic predetermination operating in concert with or independent of hemodynamic cues, particularly during development [101]. However, there is considerable arterio-venous plasticity in ECs and microvessels [102,103], suggesting that the level of genetic predetermination might be limited in the adult.…”