Valsartan regulates TGF-β/Smads and TGF-β/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure

Abstract

This study investigated the interaction among valsartan (VAL), TGF-β pathways, and long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in doxorubicin (DOX)-induced heart failure (HF), and explored their roles in DOX-induced HF progression. HF mice models in vivo were constructed by DOX induction. The expression of CHRF and TGF-β1 in hearts was detected, along with cardiac function, caspase-3 activity, and cell apoptosis. Primary myocardial cells were pretreated with VAL, followed by DOX induction in vitro for functional studies, including the detection of cell apoptosis with terminal deoxynucleotidyl transferase dUTP nick-end labeling and the expression of proteins associated with TGF-β1 pathways. HF models were established in vivo and in vitro. Expression of CHRF and TGF-β1 was up-regulated, and cell apoptosis and caspase-3 activity were increased in the hearts and cells of the HF models. VAL supplementation alleviated the cardiac dysfunction and injury in the HF process. Moreover, overexpressed CHRF up-regulated TGF-β1, promoted myocardial cell apoptosis, and reversed VAL's cardiac protective effect, while interference of CHRF (si-CHRF) did the opposite. Down-regulation of CHRF reversed the increased expression of TGF-β1 and the downstream proteins induced by pcDNA-TGF-β1 in HL-1 cells, while overexpression of CHRF reversed the VAL's cardiac protective effect in vivo. In conclusion, VAL regulates TGF-β pathways through lncRNA CHRF to improve DOX-induced HF.

Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway

“…Bcl6 is emerging as a key oncoprotein and therapeutic target with a powerful transcriptional repression effect that silences hundreds of genes (Cardenas et al, ). Recently, Bcl6 was reported to suppress renal inflammation via negatively regulating NLRP3 transcription in a human renal tubular epithelial cell line (Chen et al, ). Bcl6 also attenuates allergic airway inflammation (Seto et al, ) and inflammation in the process of atherosclerosis (Barish et al, ).…”

Protective effects of valsartan administration on doxorubicin‑induced myocardial injury in rats and the role of oxidative stress and NOX2/NOX4 signaling

“…More recently, Sakr et al ( 12 ) investigated the effect of Val on DOX-induced cardiotoxicity in rats, and found that concurrent or post-but not pre-treatment with Val attenuated DOX-induced cardiotoxicity by inhibiting oxidative stress, apoptosis and senescence. Another study reported that Val alleviated DOX-induced cardiac dysfunction via regulation of the TGF-β signaling pathway ( 13 ).…”

Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method

“…As an incurable and progressive disease, heart failure (HF) has high morbidity and mortality rates in most countries including China [ 1 ]. According to previous studies, the prevalence of HF ranges from 1% to 2% and increases among people of age 65 years and older [ 2 ].…”