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代谢组学揭示了阿司匹林和吲哚布芬在经皮腔内血管成形术后患者中的药效学作用。

Metabolomics revealed pharmacodynamic effects of aspirin and indobufen in patients after percutaneous transluminal angioplasty surgery.

作者信息

Sun Shaobo, Xun Kang, Li Damei, Bao Renjie

机构信息

Department of Nephrology, The People's Hospital of Suzhou New District, Suzhou, Jiangsu, China.

出版信息

Front Cardiovasc Med. 2024 Oct 29;11:1433643. doi: 10.3389/fcvm.2024.1433643. eCollection 2024.

Abstract

INTRODUCTION

Aspirin and indobufen are commonly used therapeutic drugs for the prevention of vascular restenosis (VR) after percutaneous transluminal angioplasty surgery. They both exhibited antiplatelet effects but molecular mechanisms underlying metabolic changes induced by them remain unclear.

METHODS

In this study, we collected plasma samples from patients on aspirin medication ( = 5), patients on indobufen medication, patients with no medication after PTA, and healthy controls (CKs) ( = 5). Our investigation aimed to reveal the metabolic processes in patients during vascular restenosis and its amelioration through drug therapy using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS

Our data showed significant alterations in amino acid and choline metabolism in patients without medication after PTA. Aspirin and indobufen were able to regulate these metabolic pathways to alleviate VR symptoms. We identified several characteristic amino acids, including pro-leu, L-citrulline, his-glu, and L-glutamate, as important biomarkers for VR assessment in patients without medication after PTA. A total of 17 and 4 metabolites involved in arginine and phenylalanine metabolism were specifically induced by aspirin and indobufen, respectively. Their expression levels were significantly regulated by aspirin or indobufen, nearly reaching normal levels.

DISCUSSION

Taken together, our identification of metabolites involved in metabolic changes affected by aspirin and indobufen medication enhances the understanding of VR pathology after PTA. This may help identify early diagnostic biomarkers and therapeutic targets.

摘要

引言

阿司匹林和吲哚布芬是经皮腔内血管成形术后预防血管再狭窄(VR)常用的治疗药物。它们均具有抗血小板作用,但二者诱导代谢变化的分子机制仍不清楚。

方法

在本研究中,我们收集了服用阿司匹林的患者(n = 5)、服用吲哚布芬的患者、经皮腔内血管成形术后未用药的患者以及健康对照者(CKs)(n = 5)的血浆样本。我们的研究旨在通过液相色谱 - 串联质谱法(LC-MS/MS)揭示血管再狭窄患者的代谢过程及其通过药物治疗的改善情况。

结果

我们的数据显示,经皮腔内血管成形术后未用药的患者氨基酸和胆碱代谢有显著改变。阿司匹林和吲哚布芬能够调节这些代谢途径以缓解VR症状。我们确定了几种特征性氨基酸,包括脯氨酸 - 亮氨酸、L - 瓜氨酸、组氨酸 - 谷氨酸和L - 谷氨酸,作为经皮腔内血管成形术后未用药患者VR评估的重要生物标志物。阿司匹林和吲哚布芬分别特异性诱导了17种和4种参与精氨酸和苯丙氨酸代谢的代谢物。它们的表达水平受到阿司匹林或吲哚布芬的显著调节,几乎达到正常水平。

讨论

综上所述,我们对受阿司匹林和吲哚布芬药物影响的代谢变化中涉及的代谢物的鉴定,增强了对经皮腔内血管成形术后VR病理的理解。这可能有助于识别早期诊断生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb7b/11554490/a868fd29e114/fcvm-11-1433643-g001.jpg

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