cGMP-dependent protein kinase I is crucial for angiogenesis and postnatal vasculogenesis.
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.


RESULTS
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 cGKIalpha leucine zipper mutant (LZM) mice as model for cGKI deficiency. LZM mice harbor a mutation in the cGKIalpha 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
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.
Aicher
Alexandra
A
Department of Internal Medicine III, JW Goethe University, Frankfurt, Germany. aicher_a@yahoo.com
Heeschen
Christopher
C
Feil
Susanne
S
Hofmann
Franz
F
Mendelsohn
Michael E
ME
Feil
Robert
R
Dimmeler
Stefanie
S
D000818:Animals; D017209:Apoptosis; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development*; D015153:Blotting, Western; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator