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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Differential microRNA expression profiles in peripheral arterial disease
Philip W Stather1, Nicolas Sylvius, John B Wild
1Department of Cardiovascular Sciences and Department of Genetics and the NIHR Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
Background:
Peripheral arterial disease (PAD) is a clinical condition caused by an atherosclerotic process affecting the arteries of the limbs. Despite major improvements in surgical endovascular techniques, PAD is still associated with high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short noncoding RNA controlling gene expression, have emerged as major regulators of multiple biological processes.
Methods And Results:
A whole-miRNA transcriptome profiling was performed in peripheral blood from an initial sample set of patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was further investigated and validated in 2 additional sample sets. Each of these 12 miRNAs exhibited good diagnostic value as evidenced by receiver operating characteristic curve analyses. Pathway enrichment analysis using predicted and validated targets identified several signaling pathways relevant to vascular disorders. Several of these pathways, including cell adhesion molecules, were confirmed by quantifying the expression level of several candidate genes regulating the initial stages of the inflammatory atherosclerotic process. The expression level of 7 of these candidate genes exhibits striking inverse correlation with that of several, if not all, of the miRNAs of the PAD-specific miRNA signature.
Conclusions:
These results demonstrate the potential of miRNAs for the diagnosis of PAD and provide further insight into the molecular mechanisms leading to the development of PAD, with the potential for future therapeutic targets.
Insights
A 12-microRNA (miRNA) signature in blood shows diagnostic potential for peripheral arterial disease (PAD). This discovery offers insights into PAD
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Peripheral arterial disease (PAD) is a significant vascular condition linked to atherosclerosis.
- Despite advancements, PAD remains a major cause of mortality and morbidity.
- MicroRNAs (miRNAs) are key gene regulators involved in various biological processes.
Purpose of the Study:
- To identify a miRNA-based signature for diagnosing PAD.
- To explore the role of miRNAs in the molecular mechanisms of PAD.
- To investigate potential therapeutic targets for PAD.
Main Methods:
- Whole-miRNA transcriptome profiling of peripheral blood samples.
- Validation of a 12-miRNA signature in independent patient cohorts.
- Receiver operating characteristic (ROC) curve analysis for diagnostic value assessment.
- Pathway enrichment analysis and candidate gene expression quantification.
Main Results:
- A specific 12-miRNA signature (let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, -363) was identified and validated.
- The identified miRNAs demonstrated significant diagnostic value for PAD.
- Pathway analysis revealed links to vascular disorders, with inverse correlations between miRNA and candidate gene expression.
Conclusions:
- miRNAs hold promise as diagnostic biomarkers for PAD.
- The study provides insights into the molecular pathogenesis of PAD.
- These findings may pave the way for novel therapeutic strategies targeting miRNAs.
Related Concept Videos
01:21Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation
01:30Peripheral Artery Disease I: Introduction