Larixyl acetate, a TRPC6 inhibitor, attenuates pressure overload ‑induced heart failure in mice

Mol Med Rep. 2024 Mar;29(3):49. doi: 10.3892/mmr.2024.13174. Epub 2024 Jan 26.ABSTRACTHeart failure is a primary cause of global mortality. In the present study, whether larixyl acetate, an inhibitor of transient receptor potential cation channel subfamily C member 6, attenuates pressure overload‑induced heart failure in mice was investigated. To test this hypothesis, a transverse aortic constriction (TAC) animal model and an angiotensin II (Ang II)‑treated H9c2 cell model were used. Cardiac and cellular structure, function and the expression levels of hypertrophy, endoplasmic reticulum (ER) stress, apoptosis, autophagy and pmTOR/mTOR related mRNAs or proteins were assessed to explore the underlying molecular mechanisms. The results indicated that treatment with TAC or Ang II leads to significant hypertrophy and dysfunction of the heart or H9c2 cells, accompanied by an increase in ER stress, apoptosis and activation of the mTOR signaling pathway, and a decrease in autophagy. The administration of larixyl acetate attenuated these impairments, which can be reversed by inhibiting autophagy through the activation of the mTOR signaling pathway. These findings suggested that larixyl acetate can effectively protect against pressure overload‑induced heart failure by enhancing autophagy and limiting ER stress and apoptosis through inhibition of the mTOR pathway.PMID:38275127 | DOI:10.3892/mmr.2024.13174
Source: Molecular Medicine Reports - Category: Molecular Biology Authors: Source Type: research