Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease.
BACKGROUND
Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Multiple factors are thought to play a role in collateral development; however, the contribution of hypoxia inducible factor-1alpha (HIF-1alpha), which is a transcriptional activator that functions as a master regulator of oxygen homeostasis, is not completely clear. It could play an important role in modulating collateral development.


OBJECTIVE
The objective of this study is to investigate the changes and significance of expression of HIF-1alpha in patients with coronary artery collaterals.


METHODS
Collateral vessels were determined in 98 patients with >or=70% narrowing of at least one coronary artery without earlier revascularization, 42 patients with coronary artery collaterals and 56 patients with no coronary artery collaterals. Extent of collaterals was expressed as scores according to the Rentrop scoring system. Another 50 cases with normal coronary arteries were selected as control. The levels of HIF-1alpha protein expression in monocyte and lymphocyte in the participants were tested by immunohistochemistry (IHC) and western blot; mRNA levels were measured using reverse transcriptase PCR technique.


RESULTS
Compared with the control with normal coronary artery, the patients had higher expression of HIF-1alpha protein tested by IHC and western blot (52.6+/-10.2 vs. 13.7+/-6.2 by IHC, 50.8+/-4.5 vs. 6.5+/-1.8 by western blot); furthermore, significantly higher HIF-1alpha expression was observed in patients with collaterals compared with patients with no collaterals (81.5+/-11.8 vs. 20.7+/-9.4 by IHC; 87.2+/-6.5 vs. 9.5+/-1.4 by western blot). On the transcriptional levels of HIF-1alpha, the result was the same as the protein, there was significant difference of HIF-1alpha between the three groups. The patients with collaterals were the highest (127.3+/-23.9), followed by patients with no collaterals (35.7+/-12.3), and the control were the lowest (23.5+/-9.3). A highly positive correlation was observed between the expression/transcription of HIF-1alpha and collateral score (P<0.01, IHC: r1=0.78, reverse transcriptase PCR: r2=0.69, western blot: r3=0.84).


CONCLUSIONS
These data suggest that higher inductions of HIF-1alpha are associated with coronary collaterals, thus implying that HIF-1alpha may promote coronary collateral formation. Detection of HIF-1alpha expression might be helpful to predict prognosis of patients with coronary artery disease.
Chen
Song-ming
SM
Department of Cardiology, First Affiliated Hospital, Shantou, Guangdong, China. csm@126.com
Li
Yu-guang
YG
Zhang
Hong-xuan
HX
Zhang
Guo-hong
GH
Long
Jia-ru
JR
Tan
Chun-jiang
CJ
Wang
Dong-ming
DM
Fang
Xiao-yi
XY
Mai
Rui-qin
RQ
D000368:Aged; D016022:Case-Control Studies; D003097:Collateral Circulation; D003324:Coronary Artery Disease / Q000097:blood*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger