Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia
Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia
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DOI：
10.1160/th17-05-0349
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发表时间：
2018-01-01
影响因子：
6.7
通讯作者：
Watanabe, Takuya
中科院分区：
文献类型：
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作者：
Kojima, Miho;Ozawa, Nana;Watanabe, Takuya
Catestatin 是一种儿茶酚胺释放抑制肽，具有多种心血管活性。最近报道了冠状动脉疾病（CAD）患者血浆中儿茶素水平升高或降低的相互矛盾的结果。然而，此前尚未有关于catestin对动脉硬化作用的报道。本研究评估了 catestin 对体外人巨噬细胞、人主动脉平滑肌细胞 (HASMC) 和人脐静脉内皮细胞 (HUVEC) 的血管保护作用，以及在载脂蛋白 E 缺陷 (ApoE(-/-)) 喂养的载脂蛋白 E 缺陷 (ApoE(-/-)) 小鼠中主动脉粥样硬化和钢丝损伤诱导的股动脉新生内膜增生。 高胆固醇饮食。比较 CAD 和非 CAD 患者冠状动脉病变中儿联蛋白的组织学表达及其血浆水平。 Catestatin 在培养的人单核细胞、巨噬细胞、HASMC 和 HUVEC 中大量表达。 Catestatin 显着抑制脂多糖诱导的 HUVEC 中肿瘤坏死因子-a、血管细胞粘附分子-1 和细胞间粘附分子-1 的上调。 Catestatin 显着抑制与酰基辅酶 A 相关的炎症反应和氧化低密度脂蛋白诱导的泡沫细胞形成：人巨噬细胞中胆固醇酰基转移酶 1 下调和 ATP 结合盒转运蛋白 A1 上调。 Catestatin 显着抑制迁移、增殖和胶原蛋白 1 表达，而不诱导细胞凋亡，并增加 HASMC 中弹性蛋白和纤连蛋白的表达。对ApoE(-/-)小鼠给予catestatin可显着延缓整个主动脉粥样硬化病变，使粥样斑块中巨噬细胞、平滑肌细胞和胶原纤维的含量下降，但对股动脉损伤引起的内膜增生没有影响。在 CAD 患者中，血浆中的儿联蛋白水平显着降低，但冠状动脉粥样斑块中的水平升高。这项研究提供了第一个证据，证明儿茶素可以预防巨噬细胞驱动的动脉粥样硬化，但不能预防血管损伤后 SMC 衍生的内膜增生。
Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E-deficient (ApoE(-/-)) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-a, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA: cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE(-/-) mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury-induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.