Emerging in diabetic cardiomyopathy: molecular pathways and targets for therapeutic intervention

Abstract

Amongst various complications presented by diabetes, diabetic cardiomyopathy (DCM) is one of the most prominent and vexing complications. Due to the absence of consensus on prevention and treatment strategies, along with limitations in current therapies, a fresh perspective is essential and a requirement of the time. The succeeding review explores research that provides insights into novel molecular targets that could possibly evolve as breakthroughs in restraining the pathological hallmarks of DCM, such as inhibition of cardiomyocyte fibrosis or modulation of various inflammatory pathways, apoptotic pathways such as PANoptosis, cuproptosis, and ferroptosis, and mitochondrial dysfunction. This review shall also explore various RNA-targeting therapeutic areas that can combat the consecution of DCM. Therapeutic intervention targeting Phosphodiesterase 4D (PDE4D), LGR6 (G-protein-coupled receptor containing leucine-rich repeats 6), Interferon gamma inducible protein 16 (IFI16), Growth differentiation factor 11(GDF11), Transcription factor EB(TFEB), Secreted frizzled-related protein 1 (SFRP1), Fibroblast growth factor -21 (FGF21), Takeda G protein-coupled receptor-5 (TGR5), Nuclear receptor of the subfamily 4 (NR4A3), Enhancer of zeste homolog 2 (EZH2), and RNA-based therapeutics such as piR112710 and TUG1 are reviewed. Moreover, how these molecular targets intersect with DCM pathology, and how they can be further explored in a drug discovery paradigm for DCM management, is discussed.