Related Experiment Video
Updated: Nov 3, 2025
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
MiR-135a Protects against Myocardial Injury by Targeting TLR4
Hui Feng1,2, Bing Xie2, Zhuoqi Zhang2
1Department of Cardiology, The First Affiliated Hospital of Soochow University.
Abstract:
Emerging evidence highlights the importance of microRNAs (miRNAs) as functional regulators in cardiovascular disease. This study aimed to investigate the functional significance of miR-135a in the regulation of cardiac injury after isoprenaline (ISO) stimulation and the underlying mechanisms of its effects. Murine models with cardiac-specific overexpression of miR-135a were constructed with an adeno-associated virus expression system. The cardiac injury model was induced by ISO injection (60 mg/kg per day for 14 d). In vitro, we used H9c2 cells to establish a cell injury model by ISO stimulation (10 µM). The results indicated that miR-135a was increased during days 0-6 of ISO injection and was then downregulated during days 8-14 of ISO injection. The expression of miR-135a was consistent with the in vivo findings. Moreover, mice with cardiac overexpression of miR-135a exhibited reduced cardiac fibrosis, lactate dehydrogenase levels, Troponin I, inflammatory response and apoptosis. Overexpression of miR-135a also ameliorated cardiac dysfunction induced by ISO. MiR-135 overexpression in H9c2 cells increased cell viability and decreased cell apoptosis and inflammation in response to ISO. Conversely, miR-135 silencing in H9c2 cells decreased cell viability and increased cell apoptosis and inflammation in response to ISO. Mechanistically, we found that miR-135a negatively regulated toll-like receptor 4 (TLR4), which was confirmed by luciferase assay. Furthermore, the TLR4 inhibitor eritoran abolished the adverse effect of miR-135 silencing. Overall, miR-135a promotes ISO-induced cardiac injury by inhibiting the TLR4 pathway. MiR-135a may be a therapeutic agent for cardiac injury.
Insights
MicroRNA-135a (miR-135a) plays a key role in regulating cardiac injury. This study shows miR-135a protects against isoprenaline-induced heart damage by inhibiting the toll-like receptor 4 pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- MicroRNA Therapeutics
Background:
- MicroRNAs (miRNAs) are crucial regulators in cardiovascular disease pathogenesis.
- Isoprenaline (ISO) is commonly used to induce cardiac injury models for research.
- Understanding specific miRNA roles, like miR-135a, is vital for developing new therapies.
Purpose of the Study:
- To investigate the functional role of miR-135a in isoprenaline-induced cardiac injury.
- To elucidate the underlying molecular mechanisms involving miR-135a in cardiac damage.
- To assess the therapeutic potential of miR-135a in cardiovascular injury.
Main Methods:
- Cardiac-specific miR-135a overexpression in murine models using adeno-associated virus vectors.
- In vivo cardiac injury induced by isoprenaline (ISO) injection.
- In vitro studies using H9c2 cells subjected to ISO stimulation and miR-135a manipulation (overexpression/silencing).
- Assessment of cardiac function, fibrosis, inflammation, and apoptosis markers.
- Luciferase assays to confirm the interaction between miR-135a and toll-like receptor 4 (TLR4).
Main Results:
- miR-135a expression levels fluctuated during ISO-induced cardiac injury.
- Overexpression of miR-135a significantly reduced cardiac fibrosis, inflammation, apoptosis, and improved cardiac function in vivo.
- In vitro, miR-135a overexpression enhanced H9c2 cell viability and reduced ISO-induced apoptosis and inflammation.
- miR-135a was found to negatively regulate toll-like receptor 4 (TLR4).
- Inhibition of TLR4 by eritoran counteracted the detrimental effects of miR-135a silencing.
Conclusions:
- miR-135a plays a protective role against isoprenaline-induced cardiac injury.
- The protective mechanism involves the inhibition of the toll-like receptor 4 (TLR4) pathway.
- miR-135a demonstrates potential as a therapeutic agent for treating cardiac injury.
