Captopril and vascular endothelial growth factor in a mouse model of retinopathy

Autor: Jotishna Sharma, Yixun Geng, Sybil M. Barr, Yun Yan, Rosemary D. Higgins
Rok vydání: 2003
Předmět:
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Captopril
Blotting
Western
Angiotensin-Converting Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Hyperoxia
Retinal Neovascularization
Mice
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Internal medicine
medicine
Animals
RNA
Messenger
Vascular Endothelial Growth Factor Receptor-1
biology
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Retinal
Kinase insert domain receptor
Angiotensin-converting enzyme
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
eye diseases
Sensory Systems
Mice
Inbred C57BL
Vascular endothelial growth factor
Disease Models
Animal
Ophthalmology
Vascular endothelial growth factor A
Endocrinology
Animals
Newborn
chemistry
biology.protein
medicine.symptom
business
Retinopathy
medicine.drug
Zdroj: Current Eye Research. 27:123-129
ISSN: 1460-2202
0271-3683
DOI: 10.1076/ceyr.27.2.123.15955
Popis: Angiotensin converting enzyme (ACE) inhibition has been shown in animal models of retinopathy and in patients with diabetes to improve retinal neovascularization. The mechanism is not clearly identified, but could potentially be mediated via vascular endothelial growth factor modification. The objective of this study was to determine the effect of captopril, an angiotensin converting enzyme (ACE) inhibitor, on retinal VEGF, VEGF-R1, and VEGF-R2 expression in a mouse model of oxygen induced retinopathy (OIR).A mouse model of OIR was used and retinal tissue was obtained at P7, prior to oxygen exposure, at P12, just after oxygen exposure, and at P17, the time of maximal retinal neovascularization for VEGF, VEGF-R1 and VEGF-R2 assessment. A group of animals were treated with captopril (0.5 mg/kg/d SC from P7 for five days).Captopril plus OIR treated animals had higher levels of retinal VEGF mRNA and protein at P12 (p0.05) and lower levels at P17 (p0.05) than OIR animals. VEGF-R1 mRNA expression increased 16 fold from P7 to P17 (p0.05) in room air reared animals. VEGF-R1 mRNA expression was unaffected by OIR and/or captopril treatment. VEGF-R2 mRNA expression decreased from P7 to P17 by 1.5-fold in room air reared animals (p = 0.001). Retinal VEGF-R2 mRNA and protein expression were significantly higher at P12 in OIR plus captopril treated animals than OIR animals (p = 0.01).In summary, captopril maintains VEGF and increases VEGF-R2 expression during the period of hyperoxia when VEGF expression is normally suppressed. Captopril treatment during oxygen exposure is associated with a reduction in the angiogenic response at day 17 as manifested by decreased VEGF and VEGF-R2 expression in retinal tissue. Angiotensin converting enzyme inhibition is associated with changes in expression of VEGF and VEGF-R2 in the evolution of retinal neovascularization in the mouse model of retinopathy.
Databáze: OpenAIRE
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