Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms.
Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms.
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DOI：
10.1016/j.npep.2010.10.002
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发表时间：
2011-02
期刊：
影响因子：
2.9
通讯作者：
Habecker BA
中科院分区：
文献类型：
--
作者：
Alston EN;Parrish DC;Hasan W;Tharp K;Pahlmeyer L;Habecker BA
心脏功能由交感神经和副交感神经传递的平衡调节。从心脏交感神经元释放的神经肽Y（NPY）和甘丙肽（GAL）抑制心脏中的副交感神经传递。交感神经肽可能导致自主神经失衡，其特征在于交感神经传递增加和副交感神经传递减少，并导致危及生命的心血管病变。心肌梗死（MI）后心脏中的几种gp 130细胞因子增加，并且这些细胞因子刺激交感神经元中的神经肽表达。我们使用交感神经元缺乏gp 130受体的小鼠（gp 130 DBHCre/lox小鼠）来询问MI后gp 130的细胞因子激活是否调节心脏交感神经中神经肽的表达。心肌梗死通过gp 130非依赖性机制降低NPY mRNA，通过gp 130增加VIP和PACAP mRNA，而GAL mRNA无变化。免疫组化显示，心肌梗死后星状神经节细胞中PACAP 38的gp 130依赖性增加，在所有基因型和手术组的节前纤维中检测到PACAP。VIP在所有基因型和手术组的少数交感神经纤维中被鉴定。GAL和PACAP 38在假心脏中未检测到，但在MI后三天的梗死中肽免疫反应性很高。令人惊讶的是，肽在与巨噬细胞标记物F4/80和MAC 2共标记的细胞中丰富，但在交感神经轴突中未检测到。PACAP保护心肌细胞免于凋亡，GAL除了抑制副交感神经传递之外还刺激轴突再生。因此，这些肽可能在缺血再灌注后心脏和神经元重塑中发挥重要作用。
Cardiac function is regulated by a balance of sympathetic and parasympathetic transmission. Neuropeptide Y (NPY) and galanin (GAL) released from cardiac sympathetic neurons inhibits parasympathetic transmission in the heart. Sympathetic peptides may contribute to autonomic imbalance, which is characterized by increased sympathetic and decreased parasympathetic transmission and contributes to life threatening cardiovascular pathologies. Several gp130 cytokines are increased in the heart after myocardial infarction (MI), and these cytokines stimulate neuropeptide expression in sympathetic neurons. We used mice whose sympathetic neurons lack the gp130 receptor (gp130DBHCre/lox mice) to ask if cytokine activation of gp130 regulated neuropeptide expression in cardiac sympathetic nerves after MI. Myocardial infarction decreased NPY mRNA through a gp130 independent mechanism and increased VIP and PACAP mRNA via gp130, while GAL mRNA was unchanged. Immunohistochemistry revealed a gp130-dependent increase in PACAP38 in cells of the stellate ganglion after MI, and PACAP was detected in pre-ganglionic fibers of all genotypes and surgical groups. VIP was identified in a few sympathetic nerve fibers in all genotypes and surgical groups. GAL and PACAP38 were not detected in sham hearts, but peptide immunoreactivity was high in the infarct three days after MI. Surprisingly, peptides were abundant in cells that co-labeled with macrophage markers F4/80 and MAC2, but were not detected in sympathetic axons. PACAP protects cardiac myocytes from apoptosis, and GAL stimulates axon regeneration in addition to inhibiting parasympathetic transmission. Thus, these peptides may play an important role in cardiac and neuronal remodeling after ischemia-reperfusion.
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