Elucidation of Molecular Biological Mechanisms for Angiogenic Proliferative Action of Heparin

去年，我们证实并报道了血管生成生长因子，血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）从心脏组织产生和释放，在心包液中积累，并且这些生长因子在缺血心肌的心包液中的浓度增加，这可能有助于侧支循环的发展。今年，我们研究了是否VEGF和bFGF从心脏释放到心包腔，以响应心肌缺血。仅急诊CABG前2 d内有严重静息心绞痛者心包液中VEGF水平升高，而因冠心病行CABG者均升高bFGF水平。我们还评估了HSP 70是否作为不具有信号序列的bFGF释放的分子伴侣。不稳定型心绞痛患者心包液中HSP 70的含量是非缺血性心脏病患者的2倍。随后，我们研究了心肌内注射bFGF联合明胶对急性冠状动脉闭塞犬侧支血管发育的影响。与安慰剂治疗的狗相比，用控释bFGF治疗的狗具有发育良好的侧支。我们的结论是，局部持续交付的血管生成生长因子成功地加速和加强侧支血管的发展。

Last year, we evidenced and reported that angiogenic growth factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were produced and released from cardiac tissue, being accumulated in pericardial fluid, and that the concentrations of these growth factors in pericardial fluid from ischemic myocardium were increased, which might contribute to collateral development. This year, we studied whether VEGF and bFGF are released from the heart in response to myocardial ischemia into the pericardial space. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency CABG,while bFGF was increased in all patients undergoing CABG for coronary artery disease. We also evaluated whether HSP 70 acts as a chaperone for the release of bFGF not having the signal sequence. The levels of HSP 70 in pericardial fluid of the patients with unstable angina was twofold higher than that of those with non-ischemic heart disease. Subsequently, we examined the effect of the intramyocardial administration of bFGF combined with gelatin on the development of collateral vessels in dogs with acute coronary occlusion. The dogs treated with control-released bFGF had well-developed collaterals compared with placebo-treated dogs. We concluded that the local sustained delivery of angiogenic growth factors successfully accelerated and potentiated the development of collateral vessels.