Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, United States.
Neuropeptides. 2011 Feb;45(1):33-42. doi: 10.1016/j.npep.2010.10.002. Epub 2010 Oct 28.
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 (gp130(DBH-Cre/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.
心脏功能受交感和副交感神经传递的平衡调节。来自心脏交感神经元的神经肽 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，其特征为交感神经增加和副交感神经减少，并导致危及生命的心血管病理。心肌梗死后心脏中几种 gp130 细胞因子增加，这些细胞因子刺激交感神经元中的神经肽表达。我们使用缺乏 gp130 受体的交感神经元的小鼠（gp130(DBH-Cre/lox) 小鼠）来询问 gp130 细胞因子激活是否调节心肌梗死后心脏交感神经中的神经肽表达。心肌梗死后通过 gp130 独立机制降低 NPY mRNA，并通过 gp130 增加 VIP 和 PACAP mRNA，而 GAL mRNA 不变。免疫组织化学显示，心肌梗死后星状神经节中的 PACAP38 呈 gp130 依赖性增加，并且在所有基因型和手术组的节前纤维中均检测到 PACAP。在所有基因型和手术组中，仅在少数交感神经纤维中鉴定出 VIP。在假手术心脏中未检测到 GAL 和 PACAP38，但肽免疫反应性在 MI 后 3 天的梗塞中很高。令人惊讶的是，肽在与巨噬细胞标记物 F4/80 和 MAC2 共标记的细胞中丰富，但在交感神经轴突中未检测到。PACAP 可保护心肌细胞免于凋亡，而 GAL 除抑制副交感神经传递外，还可刺激轴突再生。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。
