Emerging roles for vasoactive peptides in diagnostic and therapeutic strategies against atherosclerotic cardiovascular diseases.
Emerging roles for vasoactive peptides in diagnostic and therapeutic strategies against atherosclerotic cardiovascular diseases.
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DOI：
10.2174/13892037113149990064
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发表时间：
2013-08
影响因子：
2.8
通讯作者：
Takuya Watanabe;Kengo Sato;F. Itoh;Yuri Noguchi;K. Fujimoto;T. Koyama;M. Shichiri
中科院分区：
文献类型：
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作者：
Takuya Watanabe;Kengo Sato;F. Itoh;Yuri Noguchi;K. Fujimoto;T. Koyama;M. Shichiri
由动脉粥样硬化引起的冠状动脉疾病（CAD）仍然是全球最常见的死亡和发病原因，尽管其风险因素，如高血压、血脂异常和糖尿病，已被单独治疗，结局日益改善。因此，开发CAD的诊断和治疗窗口非常重要。许多经典的血管活性激素、炎性细胞因子和氧化产物都被认为是潜在的生物标志物。我们最近的研究表明，高水平的促动脉粥样硬化的血管活性剂，血清素和尾加压素II，这是有效的血管收缩剂，可以用作CAD的生物标志物。在随后的试验中，我们揭示了最近发现的肽的抗动脉粥样硬化和促动脉粥样硬化作用。抗动脉粥样硬化肽包括脂肪细胞因子脂联素、神经元生长因子heregulin-β 1（神经调节蛋白-1 I型）、肠促胰岛素激素、胰高血糖素样肽-1（GLP-1）和最近通过计算机模拟方法鉴定的肽salusin-α。细胞、动物和临床实验已经证实了致动脉粥样硬化作用，表明人脂联素、调蛋白-β 1、GLP-1和salusin-α通过下调酰基辅酶A：胆固醇酰基转移酶-1抑制巨噬细胞泡沫细胞形成，从而减轻动脉粥样硬化病变的发展。与非CAD患者相比，CAD患者血液中这些肽的循环水平显著降低。受试者工作特征曲线分析表明，salusin-α是检测四种肽中CAD最有用的生物标志物。因此，salusin-α单独或与heregulin-β 1、脂联素和/或GLP-1的各种组合是预测CAD的候选生物标志物。此外，抗动脉粥样硬化肽可能成为动脉粥样硬化性心血管疾病的有用治疗靶点。
Coronary artery disease (CAD) arising from atherosclerosis remains the most common cause of death and morbidity worldwide, although its risk factors, such as hypertension, dyslipidemia, and diabetes, have been individually treated with increasingly improved outcomes. Therefore, it is important to develop diagnostic and therapeutic windows for CAD. Many classical vasoactive hormones, inflammatory cytokines, and oxidative products have been implicated as potential biomarkers. Our recent studies have shown that high levels of the pro-atherogenic vasoactive agents, serotonin and urotensin II, which are potent vasoconstrictors, can be used as biomarkers for CAD. In subsequent trials, we unraveled anti- and pro-atherogenic roles for more recently identified peptides. Anti-atherogenic peptides include the adipocytokine adiponectin, the neuronal growth factor heregulin-β₁ (neuregulin-1 type I), the incretin hormone, glucagon-like peptide-1 (GLP-1), and a peptide recently identified by an in silico approach, salusin-α. Atherogenic roles have been demonstrated by cellular, animal, and clinical experiments, which indicate that human adiponectin, heregulin-β₁, GLP-1, and salusin-α attenuate the development of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-CoA:cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are markedly decreased in CAD patients compared with those in non-CAD patients. Receiver operating characteristic curve analyses have shown that salusin-α is the most useful biomarker for detecting CAD among the four peptides examined. Therefore, salusin-α, alone or in various combinations with heregulin-β₁, adiponectin, and/or GLP-1, is a candidate biomarker for predicting CAD. Further, anti-atherogenic peptides could potentially serve as useful therapeutic targets for atherosclerotic cardiovascular diseases.