Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease
Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease
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DOI：
10.1161/circulationaha.104.476903
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发表时间：
2005-10-04
期刊：
影响因子：
37.8
通讯作者：
Yokoyama, M
中科院分区：
文献类型：
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作者：
Ejiri, J;Inoue, N;Yokoyama, M
神经营养因子（NT）家族，包括神经生长因子NT-3和脑源性神经营养因子（BDNF），在中枢和外周神经元的存活、生长、维持和死亡中起关键作用。NTs及其受体在动脉粥样硬化病变中表达;方法和结果-为了阐明NT在冠状动脉疾病发病机制中的作用，在不稳定型心绞痛（n = 38），稳定型劳力型心绞痛（n = 45），非冠心病组24例。此外，在尸检病例和通过定向冠状动脉粥样硬化切除术的心绞痛患者中检测了BDNF在冠状动脉中的区域表达。与稳定型劳力型心绞痛和非冠状动脉疾病组相比，不稳定型心绞痛组冠状窦和主动脉之间BDNF水平的差异显著更大，但NT-3水平无差异。免疫组化结果显示BDNF在冠状动脉粥样硬化的内膜和外膜中均有表达。在粥样硬化冠状动脉中，巨噬细胞和平滑肌细胞中BDNF表达增强。重组BDNF的刺激显着增强NAD（P）H氧化酶的活性和活性氧的产生在培养的人冠状动脉平滑肌cells. Conclusions BDNF有一个重要的作用，在动脉粥样硬化和斑块不稳定性，通过激活NAD（P）H氧化酶。
Background-The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear.Methods and Results-To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n = 38), stable effort angina ( n = 45), and non-coronary artery disease ( n = 24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non-coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P) H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells.Conclusions-BDNF has an important role in atherogenesis and plaque instability via the activation of NAD( P) H oxidase.