Work

Optimization of siRNA therapeutics targeting MIAT for cardioprotection in myocardial ischemia/reperfusion injury

Year: 2025

Type: article

Abstract: . Through bioinformatics analysis, we identified conserved target sites within MIAT sequences across humans, rats, and mice. We demonstrated that siRNA targeting MIAT, particularly siMIAT-20mer-UU-3, significantly improved cell viability in human and rat myocardial cells subjected to hypoxia/reoxygenation (H/R) injury, with dose-dependent effects. Furthermore, siMIAT treatment alleviated key pathological processes, including calcium overload, oxidative stress, and mitochondrial dysfunction. In a rat MI/R model, siMIAT-20mer-UU-3 significantly reduced infarct size by 49.26%, stabilized cardiac function, and improved histopathological features. Transcriptomic analysis revealed that siMIAT modulated the cAMP/protein kinase A (PKA) and NADPH/reactive oxygen species (ROS) pathways, highlighting its role in restoring myocardial homeostasis. These findings provide strong evidence for the therapeutic potential of MIAT-targeting siRNAs in treating MI/R injury and offer a comprehensive approach to the development of RNA-based therapeutics for cardiovascular diseases.

Source: Molecular Therapy — Nucleic Acids

DOI: 10.1016/j.omtn.2025.102747

Authors: Xiao-Rong Ma, Tong-Meng Yan, Yu Pan, Zhi-Hong Jiang

Institution: Macau University of Science and Technology

Language: English

Topic: Cardiac Ischemia and Reperfusion

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,900