Wang Yongzhong, Gabrielsen Anders, Lawler Patrick R, Paulsson-Berne Gabrielle, Steinbrüchel Daniel A, Hansson Goran K, Kastrup Jens
Medical Department B, Cardiac Catheterization Laboratory, the Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark.
Microcirculation. 2006 Apr-May;13(3):187-97. doi: 10.1080/10739680600556811.
Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression.
Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors.
There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium.
These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium.
动物血管生成疗法已证实缺血心肌内有新血管生成。然而，临床蛋白质和基因血管生成试验的结果却不那么令人满意。本研究旨在调查人类慢性缺血心肌中血管生成基因的表达，以及急性缺血/心脏停搏和再灌注对其表达的影响。
在冠状动脉搭桥手术期间，从15例稳定型心绞痛患者的慢性缺血心肌和非缺血心肌中获取心肌活检组织。通过寡核苷酸微阵列和定量实时PCR评估组织样本中血管生成因子的表达。
与非缺血心肌相比，慢性缺血心肌中VEGF-A和VEGF-C mRNA的基线表达相同。再灌注增加了非缺血心肌和缺血心肌中VEGF-A和VEGF-C mRNA的基因表达。VEGF-A蛋白主要在缺血心肌中心肌细胞周围的细胞外基质中检测到。
这些数据表明，慢性冠状动脉疾病中VEGF基因治疗试验结果不明确并非由于慢性缺血心肌中VEGF预先上调。慢性缺血心肌中可能存在进一步治疗性血管生成的空间。
