Gu Xuemei, Cheng Lei, Chueng Winghong L, Yao Xinsheng, Liu Hongwei, Qi Guoqing, Li Ming
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
Mol Med. 2006 Nov-Dec;12(11-12):275-83. doi: 10.2119/2006–00039.Gu.
During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases.
在心肌梗死后的重塑过程中,新生血管形成对梗死灶床毛细血管的贡献不足以满足肥厚但仍存活的心肌增加的需求,从而导致处于危险中的存活心肌细胞进一步发生缺血性损伤。在此,我们报告了通过生物测定法从日本水杨梅中鉴定和分离出血管生成单宁(angio-T),其可诱导梗死心肌快速血管再生,并提高心肌梗死后处于危险中的存活心肌细胞的存活潜力。我们的结果表明,angio-T对上调血管生成因子的表达具有强大的双重作用,这有助于早期血管再生和保护心肌细胞免受进一步的缺血性损伤,并且可诱导抗凋亡蛋白表达,从而抑制梗死心脏中心肌细胞的凋亡死亡并限制梗死面积。超声心动图研究表明,angio-T对急性梗死心肌的治疗作用在梗死后2天伴随着显著的功能改善。这种改善持续了14天。angio-T诱导早期重建血液供应网络、防止处于危险中的心肌细胞凋亡死亡以及改善梗死后心脏功能的这些治疗特性似乎是全新的,可能为治疗缺血性心脏病的治疗性血管生成医学提供新的维度。