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Published on: September 22, 2020
MicroRNA Profile of Patients with Chronic Limb-Threatening Ischemia
Muzammil H Syed1, Abdelrahman Zamzam1, Jason Valencia1
1Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
Insights
Circulating microRNA-1827 is significantly elevated in patients with chronic limb-threatening ischemia (CLTI), a condition leading to lower-limb amputations. This finding may aid in early CLTI detection and management.
Area of Science:
- Biochemistry
- Genomics
- Vascular Biology
Background:
- Chronic limb-threatening ischemia (CLTI) is a severe vascular condition often leading to amputation.
- Early detection of CLTI is crucial for timely intervention and limb salvage.
- MicroRNAs (miRNAs) are emerging as potential biomarkers for various diseases.
Purpose of the Study:
- To identify circulating microRNAs (miRNAs) associated with chronic limb-threatening ischemia (CLTI).
- To investigate the diagnostic potential of identified miRNAs in CLTI patients.
Main Methods:
- Genome-wide plasma miRNA sequencing was performed on CLTI patients and non-peripheral artery disease (PAD) controls.
- Discovery, confirmatory, and validation phases involved next-generation sequencing (NGS) and quantitative reverse transcription PCR (qRT-PCR).
- Analysis focused on identifying differentially expressed miRNAs, specifically miRNA-1827.
Main Results:
- Genome-wide sequencing identified five differentially expressed miRNAs in CLTI patients.
- Subsequent qRT-PCR confirmed that miRNA-1827 was significantly upregulated in CLTI patients across all study phases.
- Plasma levels of miRNA-1827 showed a consistent increase (≥2-fold, p < 0.001) in CLTI cohorts compared to controls.
Conclusions:
- Circulating miRNA-1827 is a significantly elevated biomarker in patients with CLTI.
- Elevated miRNA-1827 levels may serve as a valuable indicator for the early diagnosis of CLTI.
- Further research into miRNA-1827's role could lead to novel therapeutic strategies for CLTI.
Abstract:
Chronic limb-threatening ischemia (CLTI) results in devastating complications such as lower-limb amputations. In this study, a genome-wide plasma microRNAs (miRNA) sequencing was performed to identify miRNA(s) associated with CLTI. Blood samples were collected from early stage CLTI patients (ABI < 0.9) and non-PAD controls (ABI ≥ 0.9) for 3 experiments: discovery phase (n = 23), confirmatory phase (n = 52) and validation phase (n = 20). In the discovery phase, next generation sequencing (NGS) was used to identify miRNA circulating in the plasma CLTI (n = 13) patients, compared to non-PAD controls (n = 10). Two down-regulated miRNAs (miRNA-6843-3p and miRNA-6766-5p) and three upregulated miRNAs (miRNA-1827, miRNA-320 and miRNA-98-3p) were identified (≥2-fold change). In the confirmatory phase, these 5 deregulated miRNAs were further investigated in non-PAD (n = 21) and CTLI (n = 31) patients using qRT-PCR. Only miRNA-1827 was found to be significantly upregulated (≥3-fold, p-value < 0. 001) in the CLTI group. Lastly, to minimize the influence of confounding factors, miRNA-1827 plasma levels were validated in a third cohort of CLTI patients (n = 10) matched to non-PAD controls (n = 10). Our analysis demonstrated that miRNA-1827 expression was increased in the CLTI cohort (≥2-folds, p-value < 0.001). In summary, circulating miRNA-1827 is significantly elevated in patients with CLTI.
