Microvascular growth and remodelling: the interplay between sprouting and intussusceptive angiogenic mechanisms

Abstract

Embryonic development is associated with extensive vascular growth and remodeling. We studied the developing chick kidney and lung with special attention to the interplay between sprouting and intussusceptive vascular growth modes. During inauguration, the early meso-, metanephros and the lung were characterised by extensive microvascular sprouting. By E7, E13 and E15 respectively, the vascular growth mode switched to intussusception, which contributed to rapid organ vasculature growth. A phenomenal finding was that future renal lobules arose as large glomerular tufts, supplied by large vessels, which were split into smaller intralobular feeding and draining vessels with subsequent formation of solitary glomeruli. This glomerular duplication and kidney specific angioarchitecture was achieved by intussusception, i.e., by formation of pillars in rows and their successive merging to delineate the vascular entities. In the embryonic lung, intussusceptive angiogenesis contributes to a remarkably rapid expansion of the primordial vascular plexus, which successively surrounds and encloses the primitive parabronchi. As the vasculature develops increased blood flow stimulates formation of pillars in rows, their subsequent fusion and concomitant delineation of slender, solitary vascular entities from the disorganised meshwork, thus crafting the chicken lung-specific angioarchitecture. Morphometric investigations revealed that sprouting is preponderant in the early period of development, but is subsequently contemporaneous with intussusceptive angiogenesis and is supplanted by the latter by the time of hatching. Strong VEGF-A expression was associated with the sprouting phase of angiogenesis while bFGF and PDGF-B was upregulated during the phase of intussusceptive microvascular growth. We conclude that microvascular growth and remodelling in avian kidney and lung follows an adroitly crafted pattern, which entails a precise spatiotemporal interplay between sprouting and intussusceptive angiogenic growth modes supported partly by VEGF-A, bFGF and PDGF-B.