Objective: Dysregulation of thyroid hormones is a significant contributor to cardiac dysfunction, yet the precise mechanisms linking hypothyroidism to heart impairment remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and may influence various pathophysiological processes.
Materials and methods: This study investigated the role of hub genes and lncRNAs in heart tissue under hypothyroid conditions through in silico analysis and experimental validation. Thirty mice were divided into five groups: (1) hypothyroid mice induced by daily injections of 8 mg/kg propylthiouracil (PTU) for one month (Hypo-Thy group); (2) hypothyroid mice treated with 0.4 mg/kg Selected phenolic Compounds of Hydroalcoholic extract of the aerial parts of Dorema aucheri (Herbal group); (3) hypothyroid mice undergoing endurance training (Ex group); (4) hypothyroid mice receiving both Dorema aucheri extract and endurance training (Ex+Herbal group); and (5) control mice. The expression levels of mRNAs and lncRNAs were assessed using real-time qPCR, and heart and thyroid functions were evaluated through ELISA methods.
Results: Data indicated a significant enhancement in the Sirt-1/Nrf2/IL-6/Myh7/Col1a2 signaling axis in the Ex+ Herbal group compared to other groups. The expression levels of lncRNAs, including HOTAIR, GAS5, and H19, were notably altered in hypothyroid conditions.
Conclusion: Our findings suggest that endurance training and Selected Phenolic Compounds extract may effectively modulate lncRNA expression, offering potential avenues for addressing cardiac dysfunction associated with hypothyroidism. This study underscores the importance of exploring integrative approaches to mitigate heart dysfunction linked to thyroid hormone imbalances.