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Web End = Angiogenesis (2015) 18:245254 DOI 10.1007/s10456-015-9463-8
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Web End = Cell-specic impact of nitric oxide-dependent guanylyl cyclase on arteriogenesis and angiogenesis in mice
Noomen Bettaga1 Ronald Jager1 Sarah Dnnes1 Dieter Groneberg1
Andreas Friebe1
Received: 3 November 2014 / Accepted: 16 March 2015 / Published online: 21 March 2015 Springer Science+Business Media Dordrecht 2015
Abstract Nitric oxide (NO) acts as essential regulator of vasculogenesis and angiogenesis and is critical for arteriogenesis. Whether NOs effects in vivo are mediated through NO-sensitive guanylyl cyclase (NO-GC) and thus by cGMP-dependent mechanisms has been only poorly addressed. Mice lacking NO-GC globally or specically in smooth muscle cells (SMC) or endothelial cells (EC) were subjected to two established models for arteriogenesis and angiogenesis, namely hindlimb ischemia and oxygen-induced retinopathy. Our data clearly show the involvement of NO-GC in the recovery of blood ow after hindlimb ischemia, and this effect could be attributed to NO-GC in SMC. In the retina, global deletion of NO-GC led to reduced oxygen-induced vessel loss and hypoxia-induced capillary regrowth, whereas pathological neovascularization was increased. These effects were also seen in mice with SMC-specic NO-GC deletion but not in animals lacking NO-GC in EC. Intriguingly, NO-GC was found to be strongly expressed in retinal pericytes. Our data prove the involvement of NO-GC in growth and plasticity of hindlimb and retinal vasculature after ischemic/hypoxic insult.
Keywords Vasculature cGMP Ischemia Pericyte
Signal transduction
Introduction
Nitric oxide (NO) has long been known to regulate the tissue response to ischemia by enhancing arteriogenesis, angiogenesis, and progenitor cell migration [14]. Arteriogenesis involves the enlargement of preexisting vessels (collaterals) as a result of at least three mechanisms including increased shear stress, inammation, and recruitment of progenitor cells [5, 6]. Angiogenesis, on the other hand, is dened as the sprouting of capillaries from preexisting vasculature [7]. Vessel growth can be induced by tissue hypoxia and mediated by vascular endothelial growth factor (VEGF) [810] leading to the formation of new capillaries [11]. It is well documented that VEGF leads to the initiation of a series of signaling pathways including...