LncRNAs as Therapeutic Targets for Autophagy-involved Cardiovascular Diseases: A Review of Molecular Mechanism and T herapy Strategy

Background: Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. The concept of precision medicine in CVD therapy today requires the incorporation of individual genetic and environmental variability to achieve personalized disease prevention and tailored treatment. Autophagy, an evolutionarily conserved intracellular degradation process, has been demonstrated to be essential in the pathogenesis of various CVDs. Nonetheless, there have been no effective treatments for autophagy- involved CVDs. Long noncoding RNAs (lncRNAs) are noncoding RNA sequences that play versatile roles in autophagy regulation, but much needs to be explored about the relationship between lncRNAs and autophagy-involved CVDs. Summary: Increasing evidence has shown that lncRNAs contribute considerably to modulate autophagy in the context of CVDs. In this review, we first summarize the current knowledge of the role lncRNAs play in cardiovascular autophagy and autophagy-involved CVDs. Then, recent developments of antisense oligonucleotides (ASOs) designed to target lncRNAs to specifically modulate autophagy in diseased hearts and vessels are discussed, focusing primarily on structure-activity relationships of distinct chemical modifications and relevant clinical trials. Perspective: ASOs are promising in cardiovascular drug innovation. We hope that future studies of lncRNA-based therapies would overcome existing technical limitations and help people who suffer from autophagy-involved CVDs.