Translation of PDGF cardioprotective pathways.
Translation of PDGF cardioprotective pathways.
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DOI：
10.1385/ct:3:1:27
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Xaymardan, Munira
中科院分区：
文献类型：
--
作者：
Edelberg, Jay M;Cai, Dongqing;Xaymardan, Munira
老年心脏的血管功能受损，可能是老年人缺血性心脏病发病率和死亡率增加的基础。这种血管功能障碍部分是由于衰老的心脏微血管内皮细胞中血小板衍生生长因子（PDGF）介导的途径受损。通过心肌内注射生长因子恢复这些通路可以短暂地挽救衰老的心脏血管生成。通过移植年轻的骨髓源性干细胞以促进小鼠宿主衰老的心脏血管生成功能，可以在实验上实现长期重建。此外，PDGF途径的增强具有心脏保护作用，显著降低冠状动脉闭塞后心肌损伤的程度。这些发现用于治疗缺血性心脏病的临床转化必须克服PDGF的促动脉粥样硬化作用的限制，以及针对老化的心血管系统的自体干细胞/前体细胞方法的产生。靶向生长因子和/或干细胞归巢到心脏微血管中PDGF下游基因产物的策略可以提供正反馈回路以增强心脏血管生成和保护心肌梗死，并且可以为开发用于预防和治疗与衰老相关的心血管疾病的新疗法提供基础。
Vascular function in the aging heart is impaired and may underlie the increased morbidity and mortality associated with ischemic heart disease in older individuals. This vascular dysfunction is due, in part, to impairment of platelet derived growth factor (PDGF)-mediated pathways in senescent cardiac microvascular endothelial cells. Restoration of these pathways by intramyocardial injection of growth factor transiently rescues senescent cardiac angiogenesis. Longer-term reconstitution can be achieved experimentally by transplantation of young bone marrow-derived stem cells to promote senescent cardiac angiogenic function in the murine host. Moreover, enhancement of PDGF pathways is cardioprotective, markedly reducing the extent of myocardial injury following coronary occlusion. The clinical translation of these findings for treatment of ischemic heart diseases must overcome the limitation of the proatherosclerotic actions of PDGF, as well as the generation of autologous stem/precursor cell approaches, for the aging cardiovascular system. Strategies targeting growth factor and/or stem-cell homing to gene products downstream of PDGF in the cardiac microvasculature may provide positive feedback loops to enhance cardiac angiogenesis and protection from myocardial infarction and may offer a foundation for developing novel therapies for the prevention and treatment of cardiovascular disease associated with aging.