Ricardo Gutiérrez

Universidad de La Laguna

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Lucio Díaz‐Flores

Universidad de La Laguna

Juan Francisco Madrid

Universidad de Murcia

Miriam González‐Gómez

Universidad de La Laguna

José Luís Carrasco

Universidad de La Laguna

F. Valladares

Instituto de Salud Carlos III

HÁ

Hugo Álvarez‐Argüelles

Universidad de La Laguna

Francisco José Sáez

University of the Basque Country

H Varela

University of Pittsburgh

Pablo Martín‐Vasallo

Universidad de La Laguna

Maria Pino García

Hospiten Group

Cooperative Institutions

Universidad de La Laguna

Hospital Universitario de Canarias

Hospital San Agustin

Universidad Autónoma de Madrid

Marqués de Valdecilla University Hospital

Hospital Universitario Fundación Jiménez Díaz

Hospiten Group

Hospital Universitario de La Princesa

The University of Texas MD Anderson Cancer Center

Universidad de Cantabria

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Participation of Intussusceptive Angiogenesis in the Morphogenesis of Lobular Capillary Hemangioma

Scientific Reports (2020)

Lucio Díaz‐Flores Ricardo Gutiérrez Miriam González‐Gómez María-del-Pino García José Luís Carrasco

Abstract In lobular capillary hemangioma (LCH), misnamed pyogenic granuloma, only sprouting angiogenesis (SA) has been considered. We assess the occurrence of intussusceptive angiogenesis (IA) in LCH and whether IA determines the specific and other focal patterns in the lesion. For this purpose, we study specimens of 120 cases of LCH, using semithin sections (in 10), immunohistochemistry, and confocal microscopy (in 20). In addition to SA, the results in LCH showed (1) intussusceptive phenomena, including pillars/folds and associated vessel loops, which encircled interstitial tissue structures (ITSs). (2) Two types of evolved loops depending on interendothelial contacts from opposite walls: (a) numerous interendothelial contacts, alternating with capillary-sized lumens (main capillary pattern of the lesion) and (b) few interendothelial contacts, wide open lumens, and intravascular transport of pillars/folds, which were arranged linearly, forming septa (focal sinusoidal-like pattern) or were irregularly grouped (focal intravascular papillary endothelial hyperplasia, IPEH-like pattern). In conclusion, we demonstrate that IA participates in synergistic interaction with SA in LCH development and that the prevalence of specific intussusceptive phenomena determines the predominant capillary pattern and associated sinusoidal hemangioma-like and IPEH-like patterns in the lesion, which suggest a role of IA as conditioner of vessel tumour/pseudo-tumour morphology.

Capillary hemangioma

Histogenesis

10.1038/s41598-020-61921-3

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Citations (18)

Intense vascular sprouting from rat femoral vein induced by prostaglandins E1 and E2

The Anatomical Record (1994)

Lucio Díaz‐Flores Ricardo Gutiérrez Francisco Valladares Hilda Varela M. A. Pérez

Abstract The formation of new capillaries from the rat femoral vein was specifically explored to assess whether venous vessels of this caliber may participate in the process of angiogenesis. Prostaglandins of the E series (PGE1 and PGE2) were administered into the soft connective tissue surrounding the rat femoral vessels as angiogenic inducers. In these conditions, between 2 and 7 days, a great number of new capillaries were observed in the media of the femoral vein, arising from the endothelial cells (EC) in the intima. The events of the capillary growth from the femoral vein included EC activation, local degradation of the basal membrane followed by migration and proliferation of EC, solid sprout formation with posterior canalization, development of a new basal membrane, and appearance of pericytes around the new capillary. Although numerous vascular buds were also observed arising from the small venules and capillaries in the periadventitial tissues, they were separated at first from those in the media of the femoral vein by the venous adventitia. Later, connections were observed between both newly formed microcirculations. The present study shows the capacity of PGE1 and PGE2 in the extravascular position of inducing capillary sprouting from veins. Furthermore, the observations provide greater evidence that vessels with characteristics similar to those of the rat femoral vein may contribute to angiogenesis, on occasion with an intense neovascularization. This fact may be of interest for the establishment of a functional circulation after angiogenesis by anastomoses of the new capillaries with those arising from pre‐existing vessels of greater caliber than the venules. © 1994 Wiley‐Liss, Inc.

Adventitia

Femoral vein

10.1002/ar.1092380109

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Behavior of postcapillary venule pericytes during postnatal angiogenesis

Journal of Morphology (1992)

Lucio Díaz‐Flores Ricardo Gutiérrez Hilda Varela

Abstract Autogeneic bone marrow was implanted into an artificially created cavity in a segment of rat sciatic nerve, after removal of nerve fascicles, without damaging the epineurium or surrounding microcirculation. Under these conditions, the bone marrow induces capillary growth and forms granulation tissue from surrounding tissues, the behavior of pericytes being studied in the preformed (preexisting) postcapillary venules of the latter. Beginning 20 h after bone marrow implantation, the pericytes of the preexisting postcapillary venules hypertrophy, with shortening of their processes, prominent nucleoli, dispersal of ribosomes into their free form, fragmentation of basal lamina, and increased DNA synthesis. The number of contact surfaces between pericytes and endothelium is noticeably lower than in controls. Many pericytes are in mitosis. Cells with a shape transitional between pericytes and interstitial fibroblast‐like cells appear. In some cases, Monastral Blue (MB) was used as a marker of the cells in preexisting venule walls of the graft bed. In the earlier stages of the experiment, the MB labelling is restricted to the cytoplasm of pericytes and endothelial cells of postcapillary venules, and to the macrophages that occur in the space between pericytes and endothelium. Furthermore, the marker continues to be observed, at a later stage, in some of the following cells: pericytes and endothelial cells of the newly formed vessels, macrophages migrating into the interstitium, transitional cells between pericytes and fibroblasts, and typical fibroblasts of the granulation tissue. The present study provides greater evidence that preformed microvasculature pericytes are substantially activated during postnatal angiogenesis and granulation tissue formation, suggesting that they may contribute to the origin of new pericytes and fibroblasts. © 1992 Wiley‐Liss, Inc.

Pericyte

Venule

Granulation tissue

10.1002/jmor.1052130105

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Inducible perivascular cells contribute to the neochondrogenesis in grafted perichondrium

The Anatomical Record (1991)

Lucio Díaz‐Flores Ricardo Gutiérrez Pilar González Hilda Varela

Autogeneic perichondrium was implanted above the cremaster muscle of the rat, and the new formation of two types of cartilage (types I and and II) was confirmed. Also, granulation tissue was observed before the type II cartilage formation. Under these conditions, the contribution to the neocartilage of graft bed derived cells, mainly of the venule pericytes, was studied. To follow the pericyte lineage, we used a marker--Monastral Blue B--the administration of which was based on the principle of vascular labeling. While the perichondrium was kept free, before its implantation, the preformed (preexisting) venules in the cremaster muscle were exclusively labeled with Monastral Blue B, which was incorporated into the cytoplasm of pericytes and endothelial cells. After perichondrium implantation, the following sequence in tracer distribution was demonstrated. During the earlier stages, labeling was restricted to the pericytes and endothelial cells of venules in the graft bed. Later the tracer was observed in some endothelial cells and pericytes of the growing vessels and in fibroblast-like cells of the granulation tissue. Finally, some type II neochondrocytes appeared labeled. Tracer was not found in type I neochondrocytes. The presence of label in type II neochondrocytes demonstrates that they arise from progenitor cells present in the graft bed, principally from small venule pericytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Perichondrium

Venule

Pericyte

Cremaster muscle

10.1002/ar.1092290102

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Piecemeal Mechanism Combining Sprouting and Intussusceptive Angiogenesis in Intravenous Papillary Formation Induced by PGE2 and Glycerol

The Anatomical Record (2017)

Lucio Díaz‐Flores Ricardo Gutiérrez Maria del Pino García Francisco José Sáez Lucio Díaz‐Flores

ABSTRACT Recently, we demonstrated that in human intravascular papillary endothelial hyperplasia (IPEH), vein wall vascularization occurs in association with myriad papillae, a large part of which formed in the vascularized vein wall. Previously, using an animal model, we observed that PGE2 and glycerol administration around the femoral vein originates intense vascularization of the vein wall from its intimal endothelial cells (ECs). This vascularization is similar to that in IPEH. The aim of this study is to assess the mechanism of papillary formation, using this model after demonstrating papillary development in neo‐vascularized femoral vein walls. In semithin and ultrathin sections, the sequential vascular and papillary development was as follows: (a) activation of vein intimal ECs, (b) sprouting of intimal ECs towards the vein media layer and microvessel development, (c) interconnection between neighboring microvessels originated elementary loops, which encircled vein wall components and formed papillae. The encircling ECs formed the papillary cover, and the encircled component formed the core. The papillae showed a similar structure to that of folds and pillars in intussusceptive angiogenesis, and (d) origin of secondary and complex loop systems by interconnection of neighboring elementary loops and by splitting of papillae by new loops, with abundant papillary development. In conclusion, the results support a piecemeal angiogenic mechanism in papillary formation, with association of sprouting and intussusceptive types of angiogenesis. Further studies are needed to assess whether the intravascular papillae described in several pathologic processes, including vessel tumors, such as Dabska's tumor, retiform hemangioendothelioma, and angiosarcoma, follow a similar mechanism. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1781–1792, 2017. © 2017 Wiley Periodicals, Inc.

Sprouting

10.1002/ar.23599

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Role Of The Type 2 Alveolar Epithelial Cells In An Experimental Model Of Acute Lung Injury

Sonia García-Hernández Ricardo Gutiérrez Lucio Díaz‐Flores Jesús Villar Francisco Valladares

Diffuse alveolar damage

Alveolar Epithelium

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6317

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Contribution of the proximal and distal nerve stumps to peripheral nerve regeneration in silicone chambers.

PubMed (1995)

Lucio Díaz‐Flores Ricardo Gutiérrez H Varela P. Evora F. Valladares

The specific contribution of the proximal and distal nerve stumps across an 8 mm gap within silicone chamber regeneration models was studied. For this, proximal and distal (Group A), distal and distal (Group B) and proximal and proximal (Group C) nerve stumps were placed in opposite ends of silicone chambers. In all the groups, a tissue cable forms between the nerve stumps, demonstrating that, without distinction, proximal or distal stumps can stimulate the growth of other proximal or distal stumps. Furthermore, in Group B, the newly formed pseudo-nerve, in the absence of regenerating axons, contains a number of Schwann cells significantly similar to Group A, which confirms that proliferation and migration of Schwann cells do not require axonal presence or contact. Likewise, the findings demonstrate that, with the exception of the axons, the distal stump contributes to the peripheral nerve regeneration in the same way as the proximal stump. Finally, when proximal stumps are placed in both the opposite ends of the silicone chamber, Schwann cells and regenerating axons grow into the chamber gap from both inserts, and myelination also proceeds from both ends to the centre of the chambers.

Schwann cell

Epineurial repair

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Cell contribution of vasa-vasorum to early arterial intimal thickening formation.

PubMed (2007)

Lucio Díaz‐Flores Juan Francisco Madrid Ricardo Gutiérrez H Varela F. Valladares

In occluded femoral artery segments, intimal thickening occurred and abundant neovascularization from the surrounding microcirculation developed. Under these conditions, the contribution of vasa-vasorum as a source of supplementary population of cells during the early intimal thickening formation was studied. Using a technique that specifically labels venules, predominantly postcapillary venules, a marker-Monastral Blue B-was used as a tracer to follow the pericyte, endothelial cell and monocyte/macrophage lineages. In the first two days of the experiment, the marker was restricted to the wall of the periarterial microcirculation, being incorporated by endothelial cells, pericytes and some monocytes/macrophages crossing the venule walls. Later, the marker continues to be observed in some of the following cells: endothelial cells and pericytes of the newly-formed vessels, fibroblast-like cells, transitional cells between pericytes and fibroblast-like cells, macrophages migrating into the interstitium, myointimal cells and neoendothelial cells of the arterial lumen. These findings provide evidence that, during arterial intimal thickening formation in occluded arterial segments, the periarterial microvascularization contributes, in addition to recruited macrophages, newly-formed endothelial cells and a supplementary population of fibroblast-like cells and myointimal cells.

Vasa vasorum

Pericyte

Venule

Mural cell

Lumen (anatomy)

Adventitia

10.14670/hh-22.1379

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Citations (8)

Hemangioendotelioma epitelioide de pene

Actas Urológicas Españolas (2004)

Ricardo Gutiérrez J.M. Capdevila Hernández F.J. Pérez García J.M. Lanzas Prieto J. Pinto Blázquez