Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation
Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation
复制标题
DOI：
10.1152/ajpheart.01341.2008
复制
发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Quertermous, Thomas
中科院分区：
文献类型：
--
作者：
Leeper, Nicholas J.;Tedesco, Maureen M.;Quertermous, Thomas
Leeper NJ，Tedesco MM，Kojima Y，Schultz GM，Kundu RK，阿什阿什利EA，Tsao PS，Dalman RL，Quertermous T. Apelin通过抑制巨噬细胞炎症来预防主动脉瘤形成。Am J Physiol Heart Circ Physiol 296：H1329-H1335，2009.首次发表于2009年3月20日; doi：10.1152/ajpheart.01341.2008。Apelin是一种有效的血管扩张剂，最近被描述为具有抗动脉粥样硬化特性。我们假设爱帕琳肽也可能通过限制疾病相关的血管壁炎症来减弱腹主动脉瘤（AAA）的形成。用胰腺弹性蛋白酶处理植入有填充有爱帕琳肽或盐水的渗透泵的C57 BL/6小鼠以产生肾下AAA。对小鼠实施安乐死以进行主动脉PCR分析，或进行超声检查，然后实施安乐死以进行组织学分析。还在培养的巨噬细胞、平滑肌细胞和成纤维细胞中评估了响应于爱帕琳肽的炎性细胞因子和趋化因子的细胞表达。Apelin治疗导致AAA形成减少，与生理盐水治疗组相比，最大横截面积减少47%（0.74 vs. 1.39 mm（2），P < 0.03），巨噬细胞浸润减少57%（113 vs. 261.3个细胞/高倍视野，P < 0.0001）。Apelin输注还与主动脉巨噬细胞集落刺激因子表达显著降低以及单核细胞趋化蛋白（MCP）-1、巨噬细胞炎性蛋白（MIP）-1 α、白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α平均mRNA水平降低相关。Apelin刺激培养的巨噬细胞显著降低MCP-1和TNF-α mRNA水平（分别降低2.03倍和1.89倍，P < 0.03），但不影响内膜粘附分子表达或中膜或外膜细胞因子产生。Apelin显著减少人AAA疾病的弹性蛋白酶模型中的动脉瘤形成。其机制似乎是减少巨噬细胞负荷，可能与apelin介导的促炎细胞因子和趋化因子活化减少有关。
Leeper NJ, Tedesco MM, Kojima Y, Schultz GM, Kundu RK, Ashley EA, Tsao PS, Dalman RL, Quertermous T. Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation. Am J Physiol Heart Circ Physiol 296: H1329-H1335, 2009. First published March 20, 2009; doi:10.1152/ajpheart.01341.2008.-Apelin is a potent inodilator with recently described antiatherogenic properties. We hypothesized that apelin might also attenuate abdominal aortic aneurysm (AAA) formation by limiting disease-related vascular wall inflammation. C57BL/6 mice implanted with osmotic pumps filled with apelin or saline were treated with pancreatic elastase to create infrarenal AAAs. Mice were euthanized for aortic PCR analysis or followed ultrasonographically and then euthanized for histological analysis. The cellular expression of inflammatory cytokines and chemokines in response to apelin was also assessed in cultured macrophages, smooth muscle cells, and fibroblasts. Apelin treatment resulted in diminished AAA formation, with a 47% reduction in maximal cross-sectional area (0.74 vs. 1.39 mm(2), P < 0.03) and a 57% reduction in macrophage infiltrate (113 vs. 261.3 cells/high-power field, P < 0.0001) relative to the saline-treated group. Apelin infusion was also associated with significantly reduced aortic macrophage colony-stimulating factor expression and decreased monocyte chemattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha mean mRNA levels. Apelin stimulation of cultured macrophages significantly reduced MCP-1 and TNF-alpha mRNA levels relative to baseline (2.03- and 1.89-fold reduction, P < 0.03, respectively) but did not affect intimal adhesion molecule expression or medial or adventitial cell cytokine production. Apelin significantly reduces aneurysm formation in the elastase model of human AAA disease. The mechanism appears to be decreased macrophage burden, perhaps related to an apelin-mediated decrease in proinflammatory cytokine and chemokine activation.