Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy

Autor: Zhenghao Cui, David A. Sinclair, Aimee M. Juan, Dorothy T. Pei, Jean-Sébastien Joyal, Lucy P. Evans, Christian G. Hurst, Lois E.H. Smith, Przemyslaw Sapieha, Andreas Stahl, Shaday Michan, Colman J. Hatton, Jing Chen
Rok vydání: 2013
Předmět:
Retinal Ganglion Cells
Cancer Research
Physiology
Angiogenesis
Clinical Biochemistry
Carbazoles
Ischemia
Neovascularization
Physiologic
Article
Cell Line
Mice
chemistry.chemical_compound
Organ Culture Techniques
Sirtuin 1
Basic Helix-Loop-Helix Transcription Factors
medicine
Animals
Regeneration
Retinopathy of Prematurity
RNA
Messenger
Angiogenic Proteins
Mice
Knockout
Neurons
Retina
biology
Regeneration (biology)
Oxygen Inhalation Therapy
Retinal Vessels
Retinal
Anatomy
medicine.disease
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Up-Regulation
Cell biology
Mice
Inbred C57BL
Oxygen
Disease Models
Animal
medicine.anatomical_structure
Animals
Newborn
Retinal ganglion cell
chemistry
biology.protein
Protein Processing
Post-Translational
Transcription Factors
Retinopathy
Zdroj: Angiogenesis. 16:985-992
ISSN: 1573-7209
0969-6970
DOI: 10.1007/s10456-013-9374-5
Popis: Regeneration of blood vessels in ischemic neuronal tissue is critical to reduce tissue damage in diseases. In proliferative retinopathy, initial vessel loss leads to retinal ischemia, which can induce either regrowth of vessels to restore normal metabolism and minimize damage, or progress to hypoxia-induced sight-threatening pathologic vaso-proliferation. It is not well understood how retinal neurons mediate regeneration of vascular growth in response to ischemic insults. In this study we aim to investigate the potential role of Sirtuin 1 (Sirt1), a metabolically-regulated protein deacetylase, in mediating the response of ischemic neurons to regulate vascular regrowth in a mouse model of oxygen-induced ischemic retinopathy (OIR). We found that Sirt1 is highly induced in the avascular ischemic retina in OIR. Conditional depletion of neuronal Sirt1 leads to significantly decreased retinal vascular regeneration into the avascular zone and increased hypoxia-induced pathologic vascular growth. This effect is likely independent of PGC-1α, a known Sirt1 target, as absence of PGC-1α in knockout mice does not impact vascular growth in retinopathy. We found that neuronal Sirt1 controls vascular regrowth in part through modulating deacetylation and stability of hypoxia-induced factor 1α and 2α, and thereby modulating expression of angiogenic factors. These results indicate that ischemic neurons induce Sirt1 to promote revascularization into ischemic neuronal areas, suggesting a novel role of neuronal Sirt1 in mediating vascular regeneration in ischemic conditions, with potential implications beyond retinopathy.
Databáze: OpenAIRE
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