title: Cell-specific impact of nitric oxide-dependent guanylyl cyclase on arteriogenesis and angiogenesis in mice.
abstract: Nitric oxide (NO) acts as essential regulator of vasculogenesis and angiogenesis and is critical for arteriogenesis. Whether NO's 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 specifically 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 flow 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-specific 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.
authors: Physiologisches Institut, Universität Würzburg, Röntgenring 9, 97070, Würzburg, Germany.
authors: Noomen
authors: N
authors: Bettaga
authors: Ronald
authors: R
authors: Jäger
authors: Sarah
authors: S
authors: Dünnes
authors: Dieter
authors: D
authors: Groneberg
authors: Andreas
authors: A
authors: Friebe
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005091:Exons; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D000860:Hypoxia / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry; D020286:Pericytes / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000473:pathology; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D010100:Oxygen