The protective effects of Egr-1 antisense oligodeoxyribonucleotide on cardiac microvascular endothelial injury induced by hypoxia-reoxygenation.
Early growth response 1 (Egr-1) over-expression has been demonstrated in myocardial ischemia-reperfusion injury, which is closely associated with endothelial dysfunction. In the present study we investigated the expression of Egr-1 on cultured cardiac microvascular endothelial cells (CMECs) to help define the mechanism of myocardial ischemia-reperfusion injury. A model of cultured CMECs exposed to hypoxia-reoxygenation was developed in which synthesized Egr-1 sense and antisense oligodeoxyribonucleotide were transfected into the cells. The expression of Egr-1 was examined by Western blot analysis. Lactate dehydrogenase, malondialdehyde, superoxide dismutase, tumor necrosis factor alpha, and intercellular adhesion molecule 1 were measured after hypoxia-reoxygenation to assess cell function and injury. Cell morphology, cell viability, and neutrophil adhesion to the CMECs were measured to assess the degree of injury and inflammation. Only cells transfected with Egr-1 antisense oligodeoxyribonucleotide showed a significant reduction in Egr-1 protein expression following hypoxia-reoxygenation. Consistent with the down-regulation of Egr-1 expression, other forms of cell injury were significantly reduced in this group of cells, as evidenced by less alteration in cell morphology, a decrease in expression of tumor necrosis factor alpha and intercellular adhesion molecule 1, improved cell survival, and reduced neutrophil adhesion.
Zhou
Yanqiong
Y
Department of Pharmacology, Shantou University Medical College, Shantou, P.R. China.
Shi
Ganggang
G
Zheng
Jinhong
J
Huang
Zhanqin
Z
Gao
Fenfei
F
Zhang
Yanmei
Y
Guo
Fuxiao
F
Jia
Qiangyong
Q
Zheng
Yanshan
Y
D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D020319:Oligodeoxyribonucleotides, Antisense