Expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in peripheral inflammatory cells from patients with coronary heart disease.
BACKGROUND
The increased expression of heme oxygenase-1 content, a stress-response protein, directly correlates with the incidence of coronary heart disease. Down-regulation of hypoxia inducible factor-1alpha activity, a major downstream effector of the signaling pathways activated by hypoxia, increases cell survival after hypoxia. The ubiquitin system, a non-lysosomal pathway of protein degradation, is involved in processes of coronary heart disease. The aim of this study was to investigate the expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in both monocytes and lymphocytes isolated from patients at the mRNA and protein levels in different stages of coronary heart disease and their possible correlation.


METHODS
A total of 90 patients with coronary heart disease (30 acute myocardial infarction, 30 unstable angina pectoris, and 30 stable angina pectoris) were selected, and 30 cases with normal coronary artery served as controls. The mRNA and protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin in monocytes and lymphocytes were examined by semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting, respectively.


RESULTS
The mRNA expression of heme oxygenase-1 and ubiquitin was associated with the severity of coronary heart disease (p<0.05). There was no significant difference in hypoxia inducible factor-1alpha mRNA expression between the coronary heart disease patients and controls. The protein expression of heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin was significantly stronger in patients with coronary heart disease than in controls, and the expression levels increased with the severity of the disease. There was a positive association between heme oxygenase-1 and hypoxia inducible factor-1alpha and ubiquitin, antioxidative therapy with adrenergic receptor blocker, angiotensin-converting enzyme inhibitor or statins up-regulated the expression of heme oxygenase-1 and hypoxia inducible factor-1alpha.


CONCLUSIONS
These data suggest that heme oxygenase-1, hypoxia inducible factor-1alpha, and ubiquitin are involved in the development and progression of coronary heart disease and thus may be useful biomarkers for coronary heart disease.
Chen
Song-Ming
SM
Department of Cardiology, the First Affiliated Hospital, Medical College, Shantou University, Shantou Guangdong, China.
Li
Yu-Guang
YG
Wang
Dong-Ming
DM
Zhang
Guo-Hong
GH
Tan
Chun-Jiang
CJ
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D003327:Coronary Disease / Q000235:genetics* / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000235:genetics*; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000187:drug effects / Q000235:genetics*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D025801:Ubiquitin; D051547:Heme Oxygenase-1