Korean J Intern Med.  2005 Dec;20(4):295-302. 10.3904/kjim.2005.20.4.295.

Hypoxic Regulation of VEGF, HIF-1 (alpha) in Coronary Collaterals Development

• Sung KC
• Kim KS
• Lee S

• KMID: 1115253
• DOI: http://doi.org/10.3904/kjim.2005.20.4.295

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.

Keyword

VEGF; HIF-1 (alpha) ; Collaterals

MeSH Terms

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