Abstract

Unstable angina pectoris (UA) is one of the most dangerous clinical symptoms of acute coronary syndrome due to the risk of myocardial ischemia, which can lead to high morbidity and mortality worldwide. Though there are many advantages in understanding the pathophysiology of UA, the identification of biomarkers for the diagnosis, prognosis, and treatment of UA remains a challenge in the clinic. A global metabolomics research based on ultra-performance liquid chromatography (UPLC) combined with Q-TOF/MS was performed to discover the metabolic profile of health controls, UA patients, and UA patients with diabetes mellitus (DM), and screen for potential biomarkers. Twenty-seven potential biomarkers were determined using pattern recognition. These biomarkers, which include free fatty acids, amino acids, lysoPE and lysoPC species, and organic acids, can benefit the clinical diagnosis of UA. Pathway analysis indicated that arginine and proline metabolism, glycerophospholipid metabolism, and purine metabolism were affected in the UA patients, uniquely. Additionally, alterations in the metabolic signatures between UA and UA-complicated DM were also explored. As a result, six differential metabolites with an area under the curve (AUC) of more than 0.85 were identified as biomarkers for the diagnosis of UA and UA complicated with DM. Pathway analysis implied tryptophan metabolism was a key metabolic pathway in UA patients with DM, which provides new insights into the pathological study and drug discovery of UA.

Highlights

  • Unstable angina pectoris (UA), is a clinical manifestation of acute coronary syndrome (ACS), which presents as ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI)

  • A global metabolomics strategy based on ultra-performance liquid chromatography (UPLC) combined with Q-TOF/MS was used to screen for biomarkers of UA and UA complicated with diabetes mellitus (DM)

  • There were 27 and 22 plasma biomarkers identified in patients with UA and UA complicated with DM, respectively

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Summary

Introduction

Unstable angina pectoris (UA), is a clinical manifestation of acute coronary syndrome (ACS), which presents as ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). UA is more painful with longer episodes, occurs spontaneously at rest (onset angina) and more frequently, which is a progressively worsening disorder [1,2]. The current diagnosis of UA depends on symptoms interpreted by patients. These symptoms include dyspnea, vomiting, sweating, fatigue, dizziness or sudden weakness, and pain or pressure in the chest, neck, jaw, abdomen, back, shoulders, or arms. The above symptoms, which usually appear at rest, suddenly become more frequent or prolonged in UA patients, and do not change with rest or nitroglycerin. The release of myocardial necrosis enzymes during the progress is hardly detected [3].In addition, the patient’s case history

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