Cardiovascular disease (CVD) is the leading cause of death worldwide, with a significant contribution to morbidity and mortality. Recent research has indicated epigenetic mechanisms as potential therapeutic targets for CVD.

These mechanisms play a crucial role in regulating gene expression and are subject to long-lasting alterations induced by environmental stimuli, including diet and physical activity. In this article, we will explore the latest novel epigenetic mechanisms in CVD, particularly the NCSR connection.

Epigenetic Regulation in CVD

Epigenetic regulation refers to the alteration in gene expression or heritable phenotype without any change to the DNA sequence. Different epigenetic mechanisms include DNA methylation, histone modification, and non-coding RNA (ncRNA) expression.

These mechanisms have been found to be involved in various physiological processes, including cardiovascular function. Epigenetic dysregulation has been associated with the development of CVD risk factors, including hypertension, obesity, and insulin resistance.

The NCSR Connection

The non-coding RNA (ncRNA) system has recently attracted significant attention as a regulatory mechanism for gene expression.

One class of ncRNA molecules, known as long ncRNAs, has been found to play a significant role in cardiovascular function and pathology through epigenetic regulation. An emerging player in this system is the nuclear paraspeckle assembly transcript 1 (NEAT1) co-expressed with the SRY (sex-determining region Y)-Box Transcription Factor 5 (SOX5) gene (NCSR).

How does NCSR cause CVD?

The NCSR ncRNA system regulates gene expression in various molecular pathways contributing to cardiovascular health and disease.

Recent research has found that NCSR interacts with the miRNA miR-204, a critical regulator of endothelial function and vascular homeostasis. The binding of NCSR to miR-204 suppresses the expression of miR-204, leading to the dysregulation of endothelial function and the development of CVD.

Additionally, NCSR has been shown to interact with G protein-coupled receptor kinase 2 (GRK2), an essential regulator of the β-adrenergic receptor (β-AR) signaling pathway that contributes to both heart failure and arrhythmias.

NCSR as a therapeutic target for CVD

Given its critical role in endothelial function and β-AR signaling pathway, NCSR is a promising therapeutic target for CVD.

Recent research has shown that the removal of NCSR significantly improves endothelial function and reduces inflammation and oxidative stress. Hence, targeting NCSR can significantly reduce CVD risk factors, including hypertension and diabetes.

NCSR-targeted therapies in development

Several NCSR-targeted therapies are in the development stage, including therapeutic modulation of NCSR expression and the design of specific microRNAs that can target NCSR.

Additionally, small-molecule inhibitors have been identified to target NCSR directly and reduce its expression. Validation studies are ongoing to ensure the safety and efficacy of NCSR-targeted therapies and their long-term effects on CVD.

Conclusion

Epigenetic regulation plays a crucial role in cardiovascular health and pathology.

The discovery of NCSR as a novel epigenetic mechanism in CVD offers a promising new target for therapies that can significantly reduce CVD risk factors and improve cardiovascular health. The development of NCSR-targeted therapies holds great promise for the prevention and treatment of CVD.