Vascular Morphogenesis and Remodeling in a Model of Tissue Repair

Abstract

Abstract-To investigate mechanisms of vascular morphogenesis in tissue repair, we performed ovariectomy with resection of the corresponding branches of the ovarian vessels in nude mice. This induces a vascular network remodeling response in the healing ovarian pedicle. Reconstruction of 2000 histological serial sections demonstrated that a new vascular network composed of venous-venous loops forms in the wall of the dilated ovarian vein. Preexisting veins of all sizes, including a branch of the main artery, are subjected to segmentation. Loop formation and segmentation are based on intussusceptive microvascular growth. Loop formation is followed by elongation. Loop remodeling occurs also by intussusception and results in the formation of compound loop systems. All loop systems observed were completely patent. Blind-ending sprouts were extremely rare. Anastomoses between the preexisting vessels subjected to segmentation and the loop systems were established to include the newly formed vessels into the preexisting vascular network. The formation of an increasing number of patent loop systems likely decreases hypoxia and subsequently arrests angiogenesis with transformation of the granulation tissue into a scar. Loop formation also occurred inside a large thrombus that occluded a part of the lumen of the main vein.

Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance

“…It has been demonstrated in the rat (Patan et al, 1992), the chick CAM (Patan et al, 1993;Djonov et al, 2000a,b), the retina (Djonov et al, 2000a, the kidney , in a mice model of tissue repair (Patan et al, 2001a), in the human endometrium (Gargett et al, 2001;Gambino et al, 2002), in heart development (van Groningen et al, 1991), in cerebral vascularization (Zhang et al, 2002), and in tu- ), and finally the pillar tissue merges with the interstitium of the branching angle (arrows in c). d: As a result, the branching angle is relocated proximalad and the angle is altered (arrowhead).…”

“…Patan and coworkers have proposed a further mode of capillarization found in tumors. They described vascular network growth by loop formation in the vascular pedicles after ovariectomy (Patan et al, 2001a) and in grafts of LS174T human colon adenocarcinomas (Patan et al, 2001b). They propose the loops to be formed by luminal extensions, somehow like sprouts, but without their classic characteristics, in particular without endothelial cell proliferation.…”

Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease

“…This phenomenon has been described in dilated ovarian pedicle veins of nude mice after ovariectomy [Patan et al, 2001a], and in both ovariectomy and human tumor implantation [Patan et al, 2001b]. Hemorrhoidal disease presents dilated veins with secondary modifications, which can be examined by morphological and immunohistochemical procedures in numerous specimens surgically obtained from human patients.…”

Study of intussusceptive angiogenesis in inflammatory regional lymph nodes by scanning electron microscopy

“…Intussusceptive angiogenesis occurs by the division of the lumen of a preexisting vessel through the insertion of an intraluminal pillar (Patan et al, 2001). This can be clearly visualized by the analysis of corrosion models using SEM (Djonov and Burri, 2005), which is the technique used in the present study.…”