Nestin Expression by Newly Formed Human Blood Vessels

Abstract

Nestin is a type VI intermediate filament protein originally described in neural stem cells. Here we report that immature endothelial cells generated in the course of angiogenesis express nestin. Endothelial cells of embryonic capillaries destined to vascularize growing organs also express this intermediate filament protein. Whereas nestin was sporadically expressed in mature adult human endothelial cells sporadically express nestin, this protein was consistently expressed in adult angiogenic vasculature. Nestin expression was also detected in capillaries of the corpus luteum, which replenishes itself by angiogenesis. Nestin-immunoreactive vessels were also observed in the infarcted hearts where transient ischemia triggered regeneration accompanied with neovascularization of the myocardium. Nestinpositive endothelial cells lined vessels nourishing solid growing tumors, including melanoblastomas and glioblastomas. Our data provide definitive evidence that endothelial precursors express the neural stem cell marker nestin and that this protein participates in formation of the cytoskeleton of newly formed endothelial cells. Because nestin expression was recognized under all conditions of vascular development, nestin represents a novel and reliable marker of neovascularization.

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

“…Under conditions of reduced oxygen supply, WT1 is activated by HIF-1 in vascular cells (Wagner et al, 2003). More recently, we provided evidence that WT1 activates nestin, a wellknown marker of angiogenesis (Mokry et al, 2004) in cardiac and renal development (Wagner et al, 2006).…”

“…A widely accepted marker of neovascularization is the intermediate filament protein nestin, which was detected in the majority of tumour vessels and in newly forming vessels after myocardial infarction (Aihara et al, 2004;Mokry et al, 2004). Furthermore, mice expressing green fluorescent protein under control of nestin regulatory sequences are used to monitor formation of new vessels during tumour progression (Amoh et al, 2005).…”

“…As we could show recently that nestin, which is regarded as a marker of neovascularization (Aihara et al, 2004;Mokry et al, 2004), is expressed in the developing heart and kidney and regulated by WT1, we reasoned that nestin might act downstream of WT1 also in endothelial cells and in tumour vessels. Indeed, inhibition of WT1 expression by stealth RNAi significantly reduced nestin protein expression in endothelial cells as determined by western blotting ( Figure 5A).…”

“…The reduced oxygen supply in the core of the tumour (hypoxia), which results in stabilization of hypoxia-inducible factor 1 (HIF-1) and subsequent activation of its downstream target genes, has been postulated as an important factor in this process (reviewed by Semenza, 2003). A variety of other molecules, for example, VEGF, VEGF-R2, angiopoietins (reviewed by Cohen, 2006), nestin (Mokry et al, 2004) and ETS transcription factors (Wernert et al, 1992) have been implicated in tumour angiogenesis. However, the major regulatory molecules, which are involved in tumour vascularization, have not been characterized in detail so far.…”

Revisiting nestin expression in retinal progenitor cells in vitro and after transplantation in vivo

“…While nestin protein is robustly expressed in the developing CNSd in which it appears during the time of CNS stem and progenitor cell proliferation and neuronal migrationdit subsequently decreases as the brain develops (Lendahl et al, 1990;Tohyama et al, 1992;Dahlstrand et al, 1995;Kojima et al, 2004). Postnatal expression of nestin is limited to the brain subventricular (SVZ) zone and endothelial cells (Treutelaar et al, 2003;Mokry et al, 2004;Romanko et al, 2004;Ernst and Christie, 2005;Tonchev et al, 2005). Re-expression of nestin has recently been observed in activated astrocytes following various pathological conditions both in vitro and in vivo (Schmidt-Kastner and Humpel, 2002;Wei et al, 2002;Lang et al, 2004;Namba et al, 2005).…”