51. Ischemic preconditioning-mediated cardioprotection is disrupted in heterozygous Flt-1 (VEGFR-1) knockout mice
- Author
-
Sankar Addya, Guo-Hua Fong, Nilanjana Maulik, Tibor Turoczi, Fumio Yamamoto, Shoji Fukuda, Shigeaki Kaga, Saul Surrey, Keisuke Shiroto, Lijun Zhan, and Li-Juan Duan
- Subjects
Heterozygote ,Ischemia ,Myocardial Infarction ,Biology ,Mice ,Downregulation and upregulation ,Heat shock protein ,medicine ,Animals ,Ventricular Function ,RNA, Messenger ,Elméleti orvostudományok ,Receptor ,Molecular Biology ,Gene knockout ,Oligonucleotide Array Sequence Analysis ,Cardioprotection ,Mice, Knockout ,Vascular Endothelial Growth Factor Receptor-1 ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Orvostudományok ,medicine.disease ,Molecular biology ,Knockout mouse ,Immunology ,Ischemic Preconditioning, Myocardial ,cardiovascular system ,Ischemic preconditioning ,Cardiology and Cardiovascular Medicine ,Gene Deletion - Abstract
This study attempts to address an important clinical issue by identifying potential candidates of VEGF signaling through Flt-1 receptor that trigger angiogenic signal under ischemic stress. To determine the significance of VEGF-Flt-1 (VEGFR1) signaling in ischemic preconditioned (PC) myocardium, we used heterozygous Flt-1 knockout (KO) mice to dissect the pathway and identify candidate genes involved in VEGF signaling. DNA microarrays were employed to detect, characterize and distinguish altered myocardial gene expression by comparing between wild type (WT) CD-1 and heterozygous Flt-1 KO mice when exposed to ischemia (30 min) and reperfusion (2 h). Moreover, KO mice demonstrated reduced beneficial effects of PC when compared to the WT with PC. In the KO and WT mice, the % recovery of the left ventricular developed pressure and the maximum first derivative of the developed pressure after ischemia/reperfusion without PC were similar. However, when animals were subjected to PC, the left ventricular functional recovery throughout the reperfusion period was significantly lower in KO mice than in WT mice. These results indicate for the first time that in the heterozygous Flt-1 KO mice, PC is not as effective as that found in WT. This observation may be due to downregulation of several important genes such as growth-regulated oncogene 1 (Gro1), heat shock proteins (HSP), I kappa B kinase β (IKKβ), colony-stimulating factor-1 (CSF-1) and annexin A7, suggesting the importance of VEGF-Flt-1 receptor signaling during PC.
- Published
- 2005