Saturday, 17 July 2010 (Englisch)

In: Cardiovascular research   ;  87 ,  suppl_1  ;  S45-  ;  2010

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The formation of blood vessels during angiogenesis is a result of tight coordination of cell proliferation, differentiation, migration, matrix adhesion and cell-cell interplays. Notch-signalling is an intercellular pathway, which plays a central role in the establishment of patterns of gene expression, defining cell fate during development and angiogenesis. Because of ubiquitous role of the Notch receptor, we assumed that it interferes with the intussusceptive mechanism of angiogenesis. Here we have studied the effects of inhibiting Notch by the highly potent γ-secretase inhibitor (GSI) on vascular development using the chick area vasculosa (CAV), a model with rapidly growing vasculature. Our results indicated that Notch inhibition leads to formation of an immature capillary network by i) activating intussusceptive angiogenesis through robust induction of pillar formation which results in increased capillary density by more than 50%; ii) detachment of pericytes from endothelium followed by extravasation of mononuclear cells. The latter are recruited most likely to the growing transluminaly tissue pillars, i.e contribute to intussusceptive angiogenesis; iii) relatively retardation in arterial tree formation corresponding to reduction of arterial length and diameter in a range of 30-40%. The observed effects were dependant on developmental stage, applied dosage and the treatment protocol. The morphologic alterations were associated with marked downregulation of EphrinB2 transcriptional and αSMA protein levels 24 hr after GSI treatment. On transcription levels VEGFR1 demonstrated significant elevation in spite of the expression profiles of VEGFR2, bFGF and PCNA, which increased of about 2 times on average but without reaching statistically significant level. Notch inhibition caused dramatically extravasation of mononuclear cells into the perivascular space. In order to investigate the recruitment pattern, injection of fluorescently traced mouse bone- marrow-derived cells after Notch inhibition revealed spectacular induction of intussusception 4h after injection by utilisation of traced cells. All our observations assumed that Notch inhibition destroy vessel stability by disturbing maturity and alignment of pericytes. This effect is followed by invasion of progenitor cells in perivascular space, participating actively in the process of intussusceptive vascular growth. Our study is considerable progress in understanding of cellular and molecular events in intussusceptive angiogenesis. It also provide with data for molecular modulation of angiogenesis with medical relevance.

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NP
Aims and Scope
| 2010
NP-a
Editorial Board
| 2010
NP-b
Announcement: Awards Ceremony
| 2010
NP-c
Table of Contents
| 2010
S1
Welcome address
| 2010
S2
FCVB 2010 Committees
| 2010
S3
Contact Details
| 2010
S4
Congress Timetable and Floor Plan
| 2010
S6
Programme at a Glance
| 2010
S7
Final Programme
| 2010
S39
Chairpersons and Speakers Index
| 2010
S43
Friday, 16 July 2010
Popovici, M / Kobets, V / Ciobanu, N / Ivanov, V / Popovici, I / Ciobanu, L / Moraru, I / Chiusa, M / Seifriz, F / Timolati, F et al. | 2010
S45
Saturday, 17 July 2010
Dimova, I / Hlushchuk, R / Makanya, A / Djonov, V / Theurl, M / Schgoer, W / Albrecht, K / Beer, A / Patsch, J.R. / Schratzberger, P et al. | 2010
S89
Sunday, 18 July 2010
Schuchardt, M / Toelle, M / Huang, T / Wiedon, A / Van Der Giet, M / Mill, C / George, SJ / Jeremy, JY / Santulli, G / Illario, M et al. | 2010
S136
Author Index
| 2010
S146
Subject Index
| 2010