CircHECTD1 promoted MIRI-associated inflammation via inhibiting miR-138-5p and upregulating ROCK2

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Pathology

Background:

• Myocardial ischemia-reperfusion injury (MIRI) is a significant clinical challenge following cardiac events and surgeries.
• Inflammation and apoptosis are key pathological processes driving MIRI progression.
• Understanding the molecular regulators of MIRI is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of circular RNA HECTD1 (circHECTD1) in the development of MIRI.
• To elucidate the molecular mechanism involving circHECTD1, miR-138-5p, and ROCK2 in MIRI.
• To identify potential therapeutic targets for mitigating MIRI-associated inflammation and cell death.

Main Methods:

• Establishment of a rat MIRI model and assessment of infarct size using TTC staining.
• Evaluation of apoptosis via TUNEL and flow cytometry.
• Analysis of protein and RNA expression using Western blot and qRT-PCR, respectively.
• Detection of inflammatory factors using ELISA assay.
• Bioinformatic analysis and dual-luciferase assays to confirm molecular interactions.

Main Results:

• circHECTD1 and ROCK2 were upregulated, while miR-138-5p was downregulated in the MIRI model.
• Knockdown of circHECTD1 reduced H/R-induced inflammation in H9c2 cells.
• Dual-luciferase assays confirmed direct interactions: circHECTD1/miR-138-5p and miR-138-5p/ROCK2.
• circHECTD1 promoted inflammation and apoptosis by inhibiting miR-138-5p, and ROCK2 antagonized miR-138-5p's protective effects.

Conclusions:

• The circHECTD1/miR-138-5p/ROCK2 axis plays a critical role in MIRI pathogenesis.
• circHECTD1 promotes MIRI by activating ROCK2 via suppression of miR-138-5p.
• Targeting the circHECTD1 pathway may offer a novel therapeutic strategy for MIRI.