Mitochondrial ncRNAs: From Pathological Regulation to Targeted Therapy in Cardiovascular Diseases

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Mitochondrial Biology

Background:

• Heart failure (HF) is strongly associated with mitochondrial dysfunction, impacting energy metabolism, reactive oxygen species (ROS) production, and mitochondrial dynamics.
• Current therapies for mitochondrial dysfunction in HF are limited, leading to disease progression and multi-organ damage.

Purpose of the Study:

• To explore the role of mitochondrial non-coding RNAs (mt-ncRNAs) in heart failure pathogenesis.
• To investigate the therapeutic potential of targeting mitochondrial-encoded circular RNAs (mecciRNAs) and mitochondrial double-stranded RNAs (mt-dsRNAs) for HF treatment.

Main Methods:

• Review of current literature on mt-ncRNAs, mitochondrial dysfunction, and heart failure.
• Analysis of the regulatory mechanisms of mecciRNAs and mt-dsRNAs in cardiac tissue.
• Evaluation of gene therapy strategies involving mitochondrial delivery for HF.

Main Results:

• mecciRNAs play a protective role in the heart, regulating protein import, mitochondrial pores, and ROS levels. Their degradation exacerbates HF, while supplementation shows therapeutic benefits.
• mt-dsRNAs, originating from aberrant mitochondrial transcription, contribute to myocardial injury and remodeling through specific signaling pathways (MAVS, cGAS-STING, PNPT1).

Conclusions:

• mt-ncRNAs are critical regulators of mitochondrial function and HF progression.
• Gene therapy approaches targeting mecciRNAs and mt-dsRNAs, coupled with mitochondrial delivery systems, present a novel and promising therapeutic avenue for heart failure.