Neovascularization of ischemic myocardium by newly isolated tannins prevents cardiomyocyte apoptosis and improves cardiac function.
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.
Gu
Xuemei
X
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR.
Cheng
Lei
L
Chueng
Winghong L
WL
Yao
Xinsheng
X
Liu
Hongwei
H
Qi
Guoqing
G
Li
Ming
M
D043925:Angiogenesis Inducing Agents / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D031986:Geum; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D032342:Muscle Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000188:drug therapy; D009204:Myocardial Revascularization / Q000379:methods*; D010936:Plant Extracts / Q000737:chemistry*; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology*
D043925:Angiogenesis Inducing Agents; D010936:Plant Extracts; D013634:Tannins