Inflammation-induced intussusceptive angiogenesis in murine colitis.
Intussusceptive angiogenesis is a morphogenetic process that forms new blood vessels by the division of a single blood vessel into two lumens. Here, we show that this process of intraluminal division participates in the inflammation-induced neovascularization associated with chemically induced murine colitis. In studies of both acute (4-7 days) and chronic (28-31 days) colitis, intravital microscopy of intravascular tracers demonstrated a twofold reduction in blood flow velocity. In the acute colitis model, the decreased velocity was associated with marked dilatation of the mucosal plexus. In contrast, chronic inflammation was associated with normal caliber vessels and duplication (and triplication) of the quasi-polygonal mucosal plexus. Scanning electron microscopy (SEM) of intravascular corrosion casts suggested that pillar formation and septation, previously linked to the morphogenetic process of intussusceptive angiogenesis, were present within days of the onset of inflammation. Four weeks after the onset of inflammation, SEM of vascular corrosion casts demonstrated replication of the mucosal plexus without significant evidence of sprouting angiogenesis. These data suggest that mucosal capillaries have comparable aggregate cross-sectional area in acute and chronic colitis; however, there is a significant increase in functional capillary density in chronic colitis. We conclude that intussusceptive angiogenesis is a fundamental mechanism of microvascular adaptation to prolonged inflammation.
Institute of Anatomy and Cell Biology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
Moritz A
MA
Konerding
Aslihan
A
Turhan
Dino J
DJ
Ravnic
Miao
M
Lin
Christine
C
Fuchs
Timothy W
TW
Secomb
Akira
A
Tsuda
Steven J
SJ
Mentzer
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000098:blood supply* / Q000473:pathology; D016319:Corrosion Casting; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005456:Fluorescent Dyes; D018836:Inflammation Mediators / Q000633:toxicity; D007443:Intussusception / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009092:Mucous Membrane / Q000098:blood supply* / Q000473:pathology; D053758:Nanoparticles; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000502:physiology*; D013194:Staining and Labeling
D005456:Fluorescent Dyes; D018836:Inflammation Mediators