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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Altered serum microRNAs as novel diagnostic biomarkers for atypical coronary artery disease
Jun Wang1, Yinghao Pei1, Yong Zhong2
1Department of Cardiology, Jinling Hospital, School of Medicine, Nanjing University/Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu Province, P.R. China.
Insights
Researchers identified five serum microRNAs (miRNAs) as novel biomarkers for atypical coronary artery disease (ACAD). These miRNAs show potential for non-invasive diagnosis and targeted therapy for atherosclerosis and myocardial ischemia.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biomarker Discovery
Background:
- Atypical coronary artery disease (ACAD) presents diagnostic challenges due to limitations of conventional methods.
- There is a critical need for specific and sensitive biomarkers for ACAD diagnosis.
- ACAD is characterized by atypical angina or silent myocardial ischemia.
Purpose of the Study:
- To identify a novel serum microRNA (miRNA) expression profile in ACAD patients.
- To evaluate the clinical diagnostic value of identified serum miRNAs for ACAD.
- To explore potential therapeutic targets for ACAD based on miRNA expression.
Main Methods:
- Serum samples from 127 ACAD patients and 54 controls were analyzed.
- Initial miRNA screening used TaqMan Low Density Array.
- Quantitative reverse-transcription PCR (RT-qPCR) validated miRNA levels in training and validation sets.
- Bioinformatics methods predicted target genes of altered miRNAs.
Main Results:
- Five serum miRNAs (miR-487a, miR-502, miR-208, miR-215 increased; miR-29b decreased) were significantly altered in ACAD patients.
- The combined 5 serum miRNAs achieved high diagnostic accuracy (AUCs of 0.850 and 0.909).
- Predicted target genes are involved in cardiac/vascular remodeling, inflammation, and fibrosis.
Conclusions:
- The five altered serum miRNAs represent promising non-invasive biomarkers for ACAD.
- These miRNAs may serve as potential therapeutic targets for atherosclerosis and myocardial ischemia.
- The findings support the role of specific miRNA profiles in ACAD pathogenesis.
Background And Aim:
Atypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value.
Patients And Methods:
127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods.
Results:
The TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05). The area under the receiver-operating-characteristic (ROC) curve (AUC) for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001) and 0.909 (95% CI, 0.858-0.960, P<0.001) for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis.
Conclusion:
Our findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.
