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CircRNA mmu_circ_0000021 regulates microvascular function via the miR-143-3p/NPY axis and intracellular calcium
Jingjie Xiong1, Yisen Hu2, Yi Liu3
1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Abstract:
Cardiac ischemia-reperfusion (I/R) is associated with a high rate of complications. Restoring microvascular function is crucial for cardiac repair. However, the molecular mechanisms by which the circRNAs repairs microvascular dysfunction are unknown. High-throughput RNA sequencing and quantitative real-time PCR (qRT-PCR) were used to measures circRNA levels in cardiac tissue samples. We found a total of 80 up-regulated and 54 down-regulated differentially expressed circRNAs, of which mmu_circ_0000021 were consistent with bioinformatics predictions. Next, mmu_circ_0000021 knockdown and overexpression were performed to indicate the functional role of mmu_circ_0000021. The interaction of mmu_circ_0000021, miR-143-3p and NPY were evaluated using dual-luciferase assays, RNA pull-down assays and RNA immunoprecipitation (RIP). Immunohistochemistry, transmission electron microscopy, and immunofluorescence were used to determine the presence of leukocytes and changes in microvascular morphology and function. Mechanistically, mmu_circ_0000021 involved in regulating microvascular dysfunction via miR-143-3p by targeting NPY. However, the contraction of microvascular spasm caused by NPY is related to calmodulin. By regulating NPY, Circular RNA (circRNA) further affects microvascular spasm, regulates microcirculation disorders, and restores cardiac function. Our findings highlight a novel role for mmu_circ_0000021 by regulating microvascular function following I/R injury.
Insights
This study identifies a novel circular RNA, mmu_circ_0000021, that repairs microvascular dysfunction after cardiac ischemia-reperfusion injury. It regulates NPY via miR-143-3p, restoring cardiac function.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- RNA Biology
Background:
- Cardiac ischemia-reperfusion (I/R) injury leads to significant complications.
- Restoring microvascular function is critical for cardiac repair after I/R.
- The molecular mechanisms of circular RNAs (circRNAs) in repairing microvascular dysfunction remain unclear.
Purpose of the Study:
- To investigate the role of circRNAs in cardiac microvascular dysfunction following I/R injury.
- To identify specific circRNAs involved in regulating microvascular function.
- To elucidate the molecular mechanisms by which identified circRNAs impact cardiac repair.
Main Methods:
- High-throughput RNA sequencing and qRT-PCR to identify differentially expressed circRNAs.
- circRNA knockdown and overexpression studies to assess functional roles.
- Dual-luciferase assays, RNA pull-down, and RIP to analyze molecular interactions.
- Immunohistochemistry, transmission electron microscopy, and immunofluorescence to evaluate microvascular changes.
Main Results:
- Identified 80 up-regulated and 54 down-regulated circRNAs in cardiac I/R injury.
- mmu_circ_0000021 was identified as a key differentially expressed circRNA.
- mmu_circ_0000021 regulates microvascular dysfunction by targeting NPY via miR-143-3p.
- This mechanism involves regulating microvascular spasm and restoring cardiac function.
Conclusions:
- mmu_circ_0000021 plays a crucial role in mitigating cardiac microvascular dysfunction post-I/R injury.
- The identified circRNA-miRNA-mRNA axis (mmu_circ_0000021/miR-143-3p/NPY) offers a novel therapeutic target.
- Understanding this pathway is vital for developing strategies to improve outcomes after I/R injury.
