%0 Journal Article
%T cGMP-Dependent Protein Kinase I Is Crucial for Angiogenesis and Postnatal Vasculogenesis
%A Alexandra Aicher
%A Christopher Heeschen
%A Susanne Feil
%A Franz Hofmann
%A Michael E. Mendelsohn
%A Robert Feil
%A Stefanie Dimmeler
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0004879
%X Background Endothelium-derived nitric oxide plays an important role for the bone marrow microenvironment. Since several important effects of nitric oxide are mediated by cGMP-dependent pathways, we investigated the role of the cGMP downstream effector cGMP-dependent protein kinase I (cGKI) on postnatal neovascularization. Methodology/Principal Findings In a disc neovascularization model, cGKI£¿/£¿ mice showed an impaired neovascularization as compared to their wild-type (WT) littermates. Infusion of WT, but not cGKI£¿/£¿ bone marrow progenitors rescued the impaired ingrowth of new vessels in cGKI-deficient mice. Bone marrow progenitors from cGKI£¿/£¿ mice showed reduced proliferation and survival rates. In addition, we used cGKI¦Á leucine zipper mutant (LZM) mice as model for cGKI deficiency. LZM mice harbor a mutation in the cGKI¦Á leucine zipper that prevents interaction with downstream signaling molecules. Consistently, LZM mice exhibited reduced numbers of vasculogenic progenitors and impaired neovascularization following hindlimb ischemia compared to WT mice. Conclusions/Significance Our findings demonstrate that the cGMP-cGKI pathway is critical for postnatal neovascularization and establish a new role for cGKI in vasculogenesis, which is mediated by bone marrow-derived progenitors.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004879