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VEGFR1 (Flt-1+/−) gene knockout leads to the disruption of VEGF-mediated signaling through the nitric oxide/heme oxygenase pathway in ischemic preconditioned myocardium
- Source :
- Free Radical Biology and Medicine. 42:1487-1495
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- This report demonstrates that mice deficient in Flt-1 failed to establish ischemic preconditioning (PC)-mediated cardioprotection in isolated working buffer-perfused ischemic/reperfused (I/R) hearts compared to wild type (WT) subjected to the same PC protocol. WT and Flt-1+/- mice were divided into four groups: (1) WT I/R, (2) WT + PC, (3) Flt-1+/- I/R, and (4) Flt-1+/- + PC. Group 1 and 3 mice were subjected to 30 min of ischemia followed by 2 h of reperfusion and group 2 and 4 mice were subjected to four episodes of 4-min global ischemia followed by 6 min of reperfusion before ischemia/reperfusion. For both wild-type and Flt-1+/- mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the knockout mice was less compared to the WT mice even in preconditioning. The myocardial infarction and apoptosis were higher in Flt-1+/- compared to wild-type I/R. Flt-1+/- KO mice demonstrated pronounced inhibition of the expression of iNOS, p-AKT & p-eNOS. Significant inhibition of STAT3 & CREB were also observed along with the inhibition of HO-1 mRNA. Results demonstrate that Flt-1+/- mouse hearts are more susceptible to ischemia/reperfusion injury and also document that preconditioning is not as effective as found in WT and therefore suggest the importance of VEGF/Flt-1 signaling in ischemic/reperfused myocardium.
- Subjects :
- STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Nitric Oxide Synthase Type III
Heart Ventricles
Ischemia
Nitric Oxide Synthase Type II
Myocardial Reperfusion Injury
In Vitro Techniques
Biology
Nitric Oxide
Biochemistry
Article
Nitric oxide
Mice
chemistry.chemical_compound
Physiology (medical)
Internal medicine
medicine
Animals
Myocytes, Cardiac
RNA, Messenger
Elméleti orvostudományok
Cyclic AMP Response Element-Binding Protein
Mice, Knockout
Cardioprotection
Vascular Endothelial Growth Factor Receptor-1
Reverse Transcriptase Polymerase Chain Reaction
NF-kappa B
Endothelial Cells
Orvostudományok
medicine.disease
Heme oxygenase
Endocrinology
chemistry
Cytoprotection
Apoptosis
Anesthesia
Heme Oxygenase (Decyclizing)
Ischemic Preconditioning, Myocardial
Knockout mouse
cardiovascular system
Ischemic preconditioning
sense organs
Proto-Oncogene Proteins c-akt
Reperfusion injury
Heme Oxygenase-1
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....7578b388fb122bab4fc28f3fa7b44d77