Mechanisms of Macrophage Foam Cell Formation and Hypertensive Complications Caused by Vasoactive Agents

巨噬细胞泡沫细胞形成机制及血管活性药物引起的高血压并发症

• 批准号: 18590824
• 负责人: WATANABE Takuya
• 金额: $ 2.46万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590824/
• 关键词: Vasoactive Agents; Hypertension; Atherosclerosis; Complications; Urotensin ll; Salusin; Macrophage Foam Cell Formation; マクロファージ; 高血圧合併症

The present study clarified the mechanisms of macrophage foam cell formation and atherosclerosis caused by new vasoactive agents, such as urotensin II and salusins. Further, we studied the relationships between these vasoactive agents and hypertension or atherosclerotic diseases.Urotensin II, the most potent vasoconstrictor peptide to date, accelerated foam cell formation via up-regulating acyl-CoA: cholesterol acyltransferase-1 (ACAT1) inhumanmonocyte-derivedmacrophages. Urotensin II also stimulated vascular smooth muscle cell (VSMC) proliferation with synergistic effects observed when combined with serotonin, oxidized low-density lipoprotein, or reactive oxygen species. In patients with essential hypertension, plasma levels of urotensin II were positively correlated with systolic blood 〓.the same precursor (prepro-salusin), were recently discovered as new vasoactive peptides. Salusin-β exerted the potent hypotensive effects. Human macrophage foam cell formation was enhanced by salusin-β via up-regulating ACAT1, whereas was reduced by salusin-a via down-regulating ACAT1. Immunoreactive salusin-a and salusin-β were detected in human coronary atherosclerotic plaques, with dominance of salusin-β in VSMCs, fibroblasts, and macrophage-foam cells. Serum levels of salusin-a were decreased in patients with acute coronary syndrome (ACS), stable effort angina pectoris, or post myocardial infarction than in hypertensive patients or healthy volunteers. Among these groups, serum salusin-α levels were the lowest in ACS patients and their salusin-α levels were decreased in accordance with the severity of coronary artery lesions. Serum salusin-α levels in hypertensive patients were slightly lower compared with that in healthy volunteers, and were negatively correlated with the severity of carotid 〓 findings suggest that vasoactive agents modulate the progression of atherosclerosis in hypertension and may be a candidate for biomarkers of atherosclerotic diseases.

本研究阐明了巨噬细胞泡沫细胞形成和动脉粥样硬化的机制，由新的血管活性剂，如尾加压素II和salusins。尾加压素II是迄今为止最有效的血管收缩肽，它通过上调人单核细胞源性巨噬细胞的酰基辅酶A：胆固醇酰基转移酶1（ACAT 1）来促进泡沫细胞的形成。尾加压素II也刺激血管平滑肌细胞（VSMC）的增殖与协同作用时，观察到与5-羟色胺，氧化低密度脂蛋白，或活性氧。在原发性高血压患者中，血浆尾加压素II水平与收缩压呈正相关。Salusin-β具有较强的消肿作用。salusin-β通过上调ACAT 1促进人巨噬细胞泡沫细胞形成，而salusin-a通过下调ACAT 1减少人巨噬细胞泡沫细胞形成。在人冠状动脉粥样硬化斑块中检测到免疫反应性salusin-a和salusin-β，其中salusin-β在VSMC、成纤维细胞和巨噬细胞泡沫细胞中占优势。与高血压患者或健康志愿者相比，急性冠状动脉综合征（ACS）、稳定劳力型心绞痛或心肌梗死后患者血清salusin-a水平降低。ACS患者血清salusin-α水平最低，且随冠状动脉病变程度的加重而降低。高血压患者血清salusin-α水平略低于健康志愿者，且与颈动脉粥样硬化程度呈负相关。研究结果提示，血管活性药物可调节高血压患者动脉粥样硬化的进展，可能成为动脉粥样硬化疾病的候选生物标志物。

项目成果

Increased human urotensin II levels are correlated with carotid atherosclerosis in essential hypertension

• DOI: 10.1016/j.amjhyper.2006.08.001
• 发表时间: 2007-02-01
• 期刊: AMERICAN JOURNAL OF HYPERTENSION
• 影响因子: 3.2
• 作者: Suguro, Toshiaki;Watanabe, Takuya;Adachi, Mitsuru
• 通讯作者: Adachi, Mitsuru

Impact of salusin-α and -β on human macrophage foam cell formation and coronary atherosclerosis

• DOI: 10.1161/circulationaha.107.712539
• 发表时间: 2008-02-05
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Watanabe, Takuya;Nishio, Kae;Miyazaki, Akira
• 通讯作者: Miyazaki, Akira

Upregulation of acyl-coenzyme A : 〓 cyltransferase-1 by serotonin in human monocyte-derived 〓

酰基辅酶 A 的上调 : 〓 人单核细胞来源的血清素对 cyltransferase-1 的上调 〓

• 发表时间: 2006
• 作者: Watanabe;T.;Miyazaki;et. al.
• 通讯作者: et. al.

動脈硬化性疾患の予防及び治療薬の提供, 並びに動脈硬化性疾患を検出するための方法及び試薬の提供

提供动脉硬化性疾病的预防剂和治疗剂、以及检测动脉硬化性疾病的方法和试剂

• 发表时间: 2007

Increased human urotensin Il levels are correlated with carotid atherosclerosis in essential hypertension.

人尾加压素II水平升高与原发性高血压中的颈动脉粥样硬化相关。

• 发表时间: 2007
• 期刊: Am J Hypertens 20
• 作者: Suguro T;Watanabe T;et al.
• 通讯作者: et al.