Neural driven angiogenesis by overexpression of nerve growth factor

Abstract

Mechanisms regulating angiogenesis are crucial in adjusting tissue perfusion on metabolic demands. We demonstrate that overexpression of nerve growth factor (NGF) in brown adipose tissue (BAT) of NGF-transgenic mice elevates both mRNA and protein levels of vascular endothelial growth factor (VEGF) and VEGF-receptors. Increased vascular permeability, leukocyte-endothelial interactions (LEI), and tissue perfusion were measured using intravital microscopy. NGF-stimulation of adipocytes and endothelial cells elevates mRNA expression of VEGF and its receptors, an effect blocked by NGF neutralizing antibodies. These data suggest an activation of angiogenesis as a result of both: stimulation of adipozytes and direct mitogenic effects on endothelial cells. The increased nerve density associated with vessels strengthened our hypothesis that tissue perfusion is regulated by neural control of vessels and that the interaction between the NGF and VEGF systems is the critical driver for the activated angiogenic process. The interaction of VEGF- and NGF-systems gives new insights into neural control of organ vascularization and perfusion.

Proangiogenic features in chronic pelvic pain caused by adenomyosis

“…In adult female rats with surgical induction of endometriosis, the estrous dynamic changes of VEGF and NGF expression in endometrial cysts occur in parallel with changes in innervation and vascularization of the damaged tissues. It is assumed that the development of innervation in a model of endometriosis occurs through the interaction of perivascular nerve fibers accompanying the sprouting of blood vessels that vascularize the cyst [26][27][28][29].…”

Cold-Induced Changes in Gene Expression in Brown Adipose Tissue: Implications for the Activation of Thermogenesis

“…110) In adipose tissues of transgenic mice that overexpress NGF specifically in these tissues, the expression of the VEGF gene is increased. 111) This implies that NGF would enhance the expression of the VEGF gene in BAT. However, different from their effect on the VEGF gene, adrenergic and cold stimulation down-regulates the expression of the NGF gene in primary cultures of brown adipocytes and BAT of experimental animals.…”

Autologous Fat Grafting - Factors of Influence on the Therapeutic Results

“…NGF is a pentameric protein complex which neutrophic activities are mediated by the tyrosine kinase A (trkA) -high affinity receptor, specific for NGF and p75 -non-specific, low affinity receptor. Its expression in adipocytes is associated with wound healing and plasticity (Tore at al., 2007) and it exerts metabotrophic effect on glucose, lipid and energy homeostasis as well as antilipolytic, lipogenic and angiogenic effects (Emanueli et al, 2002;Hansen-Algensteadt et al, 2006). Moreover, NGF has an indirect effect on fat cells viability, proliferation and differentiation (Peeraully et al, 2004).…”