A New Mechanism for Pillar Formation during Tumor-Induced Intussusceptive Angiogenesis: Inverse Sprouting

Paku, Sándor; Dezső, Katalin; Bugyik, Edina; Tóvári, József; Tı́már, József; Nagy, Péter; László, Viktória; Klepetko, Walter; Döme, Balázs

doi:10.1016/j.ajpath.2011.05.033

Cited by 58 publications

(47 citation statements)

References 27 publications

(39 reference statements)

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“…Therefore, we suggest that, in the very specific vascular setting of the glomerulus, perivascular cells are not a driving force in the initiation of pillar formation mechanism. This is in agreement with the original hypothesis of IA [14] and the mechanism presented in tumor-induced IA [22]. Although a fully mature pillar was not identified in our samples, we can hypothesize that podocytes (glomerular perivascular cells) would be involved later in the pillar formation and subsequent vessel splitting.…”

Section: Discussionsupporting

confidence: 79%

“…During pillar maturation, interstitial tissue is involved in the pillar formation. In both physiological and pathological situations, the core of a mature pillar reveals a bundle of collagen fibers [14,22,32]. The current study demonstrated a structure resembling a mature pillar and its cross-section showed ECM covered by endothelium.…”

Section: Discussionmentioning

confidence: 72%

“…In murine ascites tumor vessels, intraluminal bridging has been described during which endothelial cytoplasmic processes extend into and across the vessel lumen, forming transluminal bridges that divide blood flow into multiple smaller-sized channels [21]. More specifically, in the vasculature of experimental subcutaneous tumors, a detailed model of vascular division due to endothelial bridging was proposed by Paku et al [22]. During this mechanism, endothelial bridges are formed and subsequently the bridge-forming endothelium attaches to a type I collagen bundle in the underlying connective tissue.…”

Section: Introductionmentioning

confidence: 99%

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Intussusceptive Pillar Formation in Developing Porcine Glomeruli

et al. 2018

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Background/Aims: Intussusceptive angiogenesis (IA) is a dynamic process which contributes to vascular expansion and remodeling. Intraluminal pillars have long been the distinctive structural indicator of IA. However, the mechanism of their formation has not been fully elucidated. Methods: Using light and electron microscopy, we studied intussusceptive vascular growth in the developing porcine metanephric kidney. Results: We observed intraluminal pillars formed by endothelial cells in the vasculature of developing glomeruli. Their diameter was < 2.5 µm, consistent with the diameter of nascent pillars. TEM revealed that the majority of these pillars consisted only of endothelium. However, a central core of extracellular matrix (ECM) covered by endothelium, reminiscent of a more mature intussusceptive pillar, was also found in the lumen of a glomerular capillary. Perivascular cells or pericytes were not involved in the pillar structure during these stages of formation. Conclusion: This study shows ECM presence in a mature intussusceptive pillar without any perivascular cell involvement in the structure. This leads to the hypothesis that ECM deposition precedes the participation of these cells in the formation of intraluminal pillars during IA in porcine metanephric glomerular capillaries.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Intussusceptive Pillar Formation in Developing Porcine Glomeruli

et al. 2018

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“…These phenomena suggest an initial phase of a piecemeal mechanism, predominantly by intussusception. Indeed, by intussusceptive angiogenesis, ECs of the vascular channels form the cover and the incarcerated components (vein wall tissue or thrombotic fibrin) form the core of structures, which partially separate from the vein wall, with subsequent transport into the vessel lumen, originating FPPs, a mechanism described as "inverse sprouting" [Paku et al, 2011] and related to "reverse intussusceptive angiogenesis" [Paku et al, 2005]. Interestingly, pathologists use the term papillae to describe structures that authors who study intussusceptive angiogenesis describe as folds and pillars.…”

Section: Role Of Vascular Loops: Formation Of Folds and Pillars -Simimentioning

confidence: 99%

Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease

Díaz‐Flores

Gutiérrez

González‐Gómez

et al. 2018

Cells Tissues Organs

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Vein segmentation is a vascular remodeling process mainly studied in experimental conditions and linked to hemodynamic factors, with clinical implications. The aim of this work is to assess the morphologic characteristics, associated findings, and mechanisms that participate in vein segmentation in humans. To this end, we examined 156 surgically obtained cases of hemorrhoidal disease. Segmentation occurred in 65 and was most prominent in 15, which were selected for serial sections, immunohistochemistry, and immunofluorescence procedures. The dilated veins showed differently sized spaces, separated by thin septa. Findings associated with vein segmentation were: (a) vascular channels formed from the vein intima endothelial cells (ECs) and located in the vein wall and/or intraluminal fibrin, (b) vascular loops formed by interconnected vascular channels (venous-venous connections), which encircled vein wall components or fibrin and formed folds/pillars/papillae (FPPs; the encircling ECs formed the FPP cover and the encircled components formed the core), and (c) FPP splitting, remodeling, alignment, and fusion, originating septa. Thrombosis was observed in some nonsegmented veins, while the segmented veins only occasionally contained thrombi. Dense microvasculature was also present in the interstitium and around veins. In conclusion, the findings suggest that hemorrhoidal vein segmentation is an adaptive process in which a piecemeal angiogenic mechanism participates, predominantly by intussusception, giving rise to intravascular FPPs, followed by linear rearrangement, remodeling and fusion of FPPs, and septa formation. Identification of other markers, as well as the molecular bases, hemodynamic relevance, and possible therapeutic implications of vein segmentation in dilated hemorrhoidal veins require further studies.

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“…This angiogenic mode is widely involved in tumor development. By using electron and confocal microscopy, Paku et al [20] observed intraluminal nascent pillars that contain a collagen bundle covered by endothelial cells (ECs) in the vasculature of experimental tumors. Tumor angiogenesis in liver metastasis from colon carcinoma is a controversial subject.…”

mentioning

confidence: 99%

Role of Notch, SDF-1 and Mononuclear Cells Recruitment in Angiogenesis

Dimova¹,

Djonov²

2017

Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

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Intussusceptive angiogenesis (IA) known also as splitting angiogenesis is a recently described mechanism of vascular growth alternative to sprouting. It plays an essential role in the vascular remodeling and adaptation of vessels during normal and pathological angiogenesis. It is an "escape" mechanism during and after irradiation and anti-VEGF therapy, both inducing angiogenic switch from sprouting to IA by formation of multiple transluminal tissue pillars. Our recently published data revealed the significant induction of IA after inhibition of Notch signaling associated with an increased capillary density by more than 50%. The induced IA was accompanied by detachment of pericytes from basement membrane, increased vessel permeability and recruitment of mononuclear cells toward the pillars; the process was dramatically enhanced after injection of bone marrowderived mononuclear cells. The extravasation of mononuclear cells with eventual bone marrow origin was associated with upregulation of chemotaxis factors SDF-1 and CXCR4. In addition, SDF-1 expression was upregulated in the endothelium of liver sinusoids in Notch1 knockout mouse, together with vascular remodeling by intussusception. In this chapter, we discuss this important mechanism of angiogenesis, as well as the role of Notch signaling, SDF-1 signaling and mononuclear cells in the complex process of angiogenesis.

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A New Mechanism for Pillar Formation during Tumor-Induced Intussusceptive Angiogenesis: Inverse Sprouting

Cited by 58 publications

References 27 publications

Intussusceptive Pillar Formation in Developing Porcine Glomeruli

Intussusceptive Pillar Formation in Developing Porcine Glomeruli

Segmentation of Dilated Hemorrhoidal Veins in Hemorrhoidal Disease

Role of Notch, SDF-1 and Mononuclear Cells Recruitment in Angiogenesis

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