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Updated: Jan 22, 2026
Induction of Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury in Mice
Published on: January 19, 2022
miR-499 released during myocardial infarction causes endothelial injury by targeting α7-nAchR
Rui Zhou1, Wenjun Huang1, Xinrong Fan2
1The Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Stockholm, Sweden.
Insights
MicroRNA-499 released from injured heart cells after acute myocardial infarction (AMI) worsens blood vessel injury by targeting alpha7-nicotinic acetylcholine receptor (α7-nAchR). This suggests miR-499 as a potential therapeutic target for post-AMI vascular inflammation.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Endothelial Function
Background:
- Acute myocardial infarction (AMI) triggers systemic inflammation, exacerbating atherosclerotic endothelial injury.
- Cardiomyocyte-derived microRNAs (miRNAs) released during AMI may play a role in endothelial damage.
- Understanding the specific mechanisms of miRNA-mediated endothelial injury post-AMI is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of miR-499, released from cardiomyocytes during AMI, in endothelial injury.
- To identify the molecular targets and pathways through which miR-499 affects endothelial cells.
- To evaluate miR-499 as a potential biomarker and therapeutic target for post-AMI vascular complications.
Main Methods:
- Quantitative PCR (qPCR) and ELISA to measure plasma miR-499 and serum thrombomodulin in AMI patients.
- In vitro studies using human umbilical vein endothelial cells (HUVECs) and rat pulmonary microvascular endothelial cells (RPMECs) exposed to AMI patient plasma or hypoxia/reoxygenation (HX/R) conditions.
- In silico analysis and cell-based assays to identify and validate miR-499 targets, including CHRNA7 (encoding α7-nAchR).
- Langendorff perfusion system to assess the impact of cardiac perfusate on vascular relaxation.
Main Results:
- Plasma miR-499 levels were significantly elevated in AMI patients and correlated with endothelial injury markers.
- AMI patient plasma and cardiomyocyte-released miR-499 exacerbated endothelial injury in vitro, an effect reversed by antagomiR-499.
- miR-499 directly targets CHRNA7, and its upregulation worsened high glucose-induced endothelial injury, while CHRNA7 overexpression ameliorated it.
- Cardiac perfusate from HX/R hearts containing elevated miR-499 impaired endothelium-dependent relaxation in rat arteries.
Conclusions:
- miR-499 released from injured cardiomyocytes contributes to endothelial injury post-AMI by targeting α7-nAchR.
- Elevated miR-499 is a potential biomarker for endothelial injury following AMI.
- Targeting miR-499 may offer a novel therapeutic strategy to mitigate vascular inflammation and endothelial dysfunction after AMI.
Abstract:
The surged systemic vascular inflammation after acute myocardial infarction (AMI) aggravates the atherosclerotic endothelial injury. To explore roles of miR-499 released from cardiomyocytes during AMI in endothelial injury. Using qPCR and ELISA, we discovered that patients with AMI had significantly increased plasma miR-499, which was directly correlated with serum thrombomodulin, a marker for endothelial injury. Plasma of AMI patients, when incubated with human umbilical vein endothelial cells (HUVECs), significantly increased the expression of endothelial injury markers, which could be abrogated by antagomiR-499. In vitro, neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation (HX/R) released miR-499 that could be internalized into rat pulmonary microvascular endothelial cells (RPMECs), worsening the high glucose-induced injury. In silico analysis demonstrated that CHRNA7 encoding α7-nAchR is a target of miR-499, which was validated in cell lines expressing endogenous α7-nAchR. In high glucose-induced RPMECs injury model, miR-499 aggravated, whereas forced CHRNA7 expression ameliorated the injury. Moreover, the perfusate from Langendorff perfused rat heart subjected to HX/R contained higher level of miR-499 that significantly impaired the Bradykinin-mediated endothelium-dependent relaxation in both conduit and resistance arteries, which could be partially abrogated by antagomiR-499. Finally, the correlation between plasma miR-499 and endothelial injury was further confirmed in another cohort of AMI patients. We conclude that miR-499 released from injured cardiomyocytes contributes to the endothelial injury by targeting α7-nAchR. This study implies that miR-499 may serve as a potential target for the treatment of the surged vascular inflammation post-AMI.
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