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Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
MicroRNA Profiling in Chronic Limb-Threatening Ischemia Their Role in Arteriogenesis
Muhamad T Ismail1, Budi Y Setianto1, Sofia M Haryana2
1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Abstract:
Chronic limb-threatening ischemia (CLTI) represents poses a substantial threat with escalating mortality and amputation rates. Despite the existence of various clinical techniques for diagnosing CLTI, the role of microRNAs (miRNAs) in arteriogenesis remains ambiguous. Comprehensive knowledge on miRNAs may facilitate the advancement of targeted therapy pertaining to the enhancement of collateral blood flow in obstructed vessels. Therefore, this study aimed at analyzing arteriogenesis-associated plasma miRNA profiles in patients with CLTI using gene expression. Samples were acquired from the collateral arteries (CA group, n = 3) and the contralateral healthy limb (healthy artery; HA group, n = 3) of a single set of patients with CLTI. The RNA extracted from the samples was assessed for concentration and purity. A normalization factor was used to address variations in analyte abundance and/or quality across the samples. Subsequently, individual RNA molecules were directly quantified and subjected to comparative analysis between the CA and HA groups to identify the miRNAs involved in arteriogenesis. The five arteriogenesis-related miRNAs exhibiting maximum upregulation were miR-301b-3p, miR-221-5p, miR-639, miR-34a-5p, and let-7a-5p, while the five most downregulated miRNAs included miR-151a-5p, miR-371a-5p, miR-651-5p, miR-510-5p, and miR-660-5p. Summarily, this study documented marked upregulation and downregulation of miRNAs associated with arteriogenesis in the collateral arteries of patients with CLTI as compared with their contralateral healthy limbs. Possible mechanisms involved, including the regulation of YAP/TAZ pathway, TGFBR3 mRNA, SIRT1 expression, and other processes have shown to be modulated by miRNAs fluctuations.
Insights
MicroRNAs (miRNAs) play a key role in arteriogenesis, the formation of new blood vessels. This study identified specific upregulated and downregulated miRNAs in patients with chronic limb-threatening ischemia (CLTI), offering potential therapeutic targets.
Area of Science:
- Vascular Biology and Medicine
- Molecular Biology
- Genomics and Bioinformatics
Background:
- Chronic limb-threatening ischemia (CLTI) is a severe condition with high mortality and amputation rates.
- Current diagnostic methods for CLTI exist, but the role of microRNAs (miRNAs) in arteriogenesis remains unclear.
- Understanding miRNA involvement in arteriogenesis could lead to targeted therapies for improving collateral blood flow.
Purpose of the Study:
- To analyze plasma microRNA (miRNA) profiles associated with arteriogenesis in patients suffering from chronic limb-threatening ischemia (CLTI).
- To identify specific miRNAs that are upregulated or downregulated in collateral arteries compared to healthy arteries in CLTI patients.
- To explore potential mechanisms, such as the regulation of YAP/TAZ pathway and TGFBR3 mRNA, modulated by miRNA fluctuations.
Main Methods:
- Collected plasma samples from collateral arteries (CA) and contralateral healthy arteries (HA) of CLTI patients.
- Assessed RNA concentration and purity, followed by normalization to account for variations.
- Quantified individual RNA molecules and performed comparative analysis between CA and HA groups to identify differentially expressed miRNAs.
Main Results:
- Identified five significantly upregulated miRNAs: miR-301b-3p, miR-221-5p, miR-639, miR-34a-5p, and let-7a-5p.
- Identified five significantly downregulated miRNAs: miR-151a-5p, miR-371a-5p, miR-651-5p, miR-510-5p, and miR-660-5p.
- Observed marked upregulation and downregulation of specific miRNAs in collateral arteries of CLTI patients compared to healthy limbs.
Conclusions:
- This study successfully documented distinct miRNA expression patterns in the collateral arteries of CLTI patients.
- The identified miRNAs are significantly associated with arteriogenesis in CLTI.
- These findings suggest that miRNA fluctuations modulate key pathways, offering potential for novel therapeutic strategies in CLTI.
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