Hypoxic Regulation of VEGF, HIF-1 (alpha) in Coronary Collaterals Development.
10.3904/kjim.2005.20.4.295
- Author:
Ki Chul SUNG
1
;
Kyung Soo KIM
;
Sang LEE
Author Information
1. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. kskim@hanyang.ac.kr
- Publication Type:Original Article
- Keywords:
VEGF;
HIF-1 (alpha);
Collaterals
- MeSH:
Vascular Endothelial Growth Factor A/*metabolism;
RNA, Messenger/metabolism;
Monocytes/metabolism;
Middle Aged;
Male;
Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism;
Humans;
Female;
*Coronary Circulation;
Coronary Arteriosclerosis/metabolism;
*Collateral Circulation;
Cells, Cultured;
Anoxia/*metabolism
- From:The Korean Journal of Internal Medicine
2005;20(4):295-302
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The interindividual variability for the development of collaterals in coronary artery disease is dependent on the hypoxic induction level of VEGF. To determine whether the hypoxic induction of VEGF is controlled by the transcription of HIF-1 (alpha), the VEGF and HIF-1 (alpha) m-RNA levels were correlated to hypoxia in monocytes harvested from patients with coronary artery disease. METHODS: The collateral scoring system used was modified from the TIMI system. The mononuclear cell layer of the patients' blood was cultured in hypoxia (1% O2, 5% CO2, 94%N2) and normoxia (5% CO2, 95% room air) for 17 hours. The VEGF and HIF-1 (alpha) mRNA levels were measured using a RT-PCR technique. We calculated the fold inductions of VEGF, HIF-1 (alpha) mRNA with hypoxia by dividing thehypoxic and the normoxic values. RESULTS: We found significantly higher hypoxic inductions of VEGF m-RNA in patients with collaterals compared to patients with no collaterals. However, there was no difference in the hypoxic inductions of HIF-1 (alpha) between the two groups (VEGF m-RNA mean fold inductions 3.71+/-3.30 versus 1.65+/-0.62, p=0.012, HIF-1 (alpha) mRNA 1.42+/-0.58 versus 1.20+/-0.39, p=0.165). CONCLUSIONS: We concluded that the interindividual variability in the hypoxic inductions of VEGF m-RNA in monocytes in patients is not controlled by the transcriptional levels of HIF-1 (alpha) with hypoxia. These findings suggest that a mechanism such as the post-transcriptional modification of HIF-1 (alpha) is involved in the hypoxic inductions of VEGF.
