No 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.The two principal and complementary forms of angiogenesis in physiological and pathological conditions are sprouting angiogenesis (SA) and intussusceptive angiogenesis (IA). In addition to microvascular growth, IA participates in vascular morphogenesis and remodelling, including vessel arborization, branching remodelling and vessel segmentation 1-11 . Hallmarks of IA are intravascular tissue pillars, which split or remodel pre-existing or newly formed vessels. Two types of pillars have been established according to diameter: small (diameter ≤ 2.5 µm) and large (diameter > 2.5 µm) pillars 10,11 . Folds, which form pillars when spanning, are also intussusceptive phenomena. Different structures have been observed in association with pillar/fold formation, including (a) endothelial contacts, symmetric (kissing contacts) or asymmetric (peg-like contacts), established between endothelial cells (ECs) of opposite vessel walls; (b) meso-like intraluminal folds; (c) merged adjacent capillaries, with modified contacting walls; and (d) vessel loops, composed of a double-sheet layer of ECs, with virtual or different sized lumens, encircling interstitial tissue structures (ITSs) 3,6,10,12,13 . Likewise, secondary structures may form from pillars and folds, as occurs with intravascular meshworks of processes, septa and pillar aggregates 5,14-16 .SA and IA are complementary mechanisms, with synergistic interaction 15,17 . In the chick chorioallantoic membrane, developmental avian kidney, lung and zebrafish caudal vein plexus, and in the rat femoral vein after PGE2 and glycerol perivenous...

Glioblastoma (GBM) is the most malignant tumor in the brain. In addition to the vascular pattern with thin-walled vessels and findings of sprouting angiogenesis, GBM presents a bizarre microvasculature (BM) formed by vascular clusters, vascular garlands, and glomeruloid bodies. The mechanisms in BM morphogenesis are not well known. Our objective was to assess the role of pericyte/endothelial proliferation and intussusceptive angiogenic mechanisms in the formation of the BM. For this purpose, we studied specimens of 66 GBM cases using immunochemistry and confocal microscopy. In the BM, the results showed (a) transitional forms between the BM patterns, mostly with prominent pericytes covering all the abluminal endothelial cell (EC) surface of the vessels, (b) a proliferation index high in the prominent pericytes and low in ECs (47.85 times higher in pericytes than in ECs), (c) intravascular pillars (hallmark of intussusceptive angiogenesis) formed by transcapillary interendothelial bridges, endothelial contacts of opposite vessel walls, and vessel loops, and (d) the persistence of these findings in complex glomeruloid bodies. In conclusion, disproportion in pericyte/EC proliferation and mechanisms of intussusceptive angiogenesis participate in BM formation. The contributions have morphogenic and clinical interest since pericytes and intussusceptive angiogenesis can condition antiangiogenic therapy in GBM.

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.