HBI-8000 improves heart failure with preserved ejection fraction via the TGF-β1/MAPK signalling pathway.
Jing TianWenjing LiLu ZengYang LiJiamin DuYing LiBin LiGuohai SuPublished in: Journal of cellular and molecular medicine (2024)
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of total heart failure patients and is characterized by peripheral circulation, cardiac remodelling and comorbidities (such as advanced age, obesity, hypertension and diabetes) with limited treatment options. Chidamide (HBI-8000) is a domestically produced benzamide-based histone deacetylase isoform-selective inhibitor used for the treatment of relapsed refractory peripheral T-cell lymphomas. Based on our in vivo studies, we propose that HBI-8000 exerts its therapeutic effects by inhibiting myocardial fibrosis and myocardial hypertrophy in HFpEF patients. At the cellular level, we found that HBI-8000 inhibits AngII-induced proliferation and activation of CFs and downregulates the expression of fibrosis-related factors. In addition, we observed that the HFpEF group and AngII stimulation significantly increased the expression of TGF-β1 as well as phosphorylated p38MAPK, JNK and ERK, whereas the expression of the above factors was significantly reduced after HBI-8000 treatment. Activation of the TGF-β1/MAPK pathway promotes the development of fibrotic remodelling, and pretreatment with SB203580 (p38MAPK inhibitor) reverses this pathological change. In conclusion, our data suggest that HBI-8000 inhibits fibrosis by modulating the TGF-β1/MAPK pathway thereby improving HFpEF. Therefore, HBI-8000 may become a new hope for the treatment of HFpEF patients.
Keyphrases
- signaling pathway
- poor prognosis
- type diabetes
- transforming growth factor
- pi k akt
- end stage renal disease
- left ventricular
- histone deacetylase
- oxidative stress
- chronic kidney disease
- ejection fraction
- blood pressure
- acute lymphoblastic leukemia
- cardiovascular disease
- newly diagnosed
- heart failure
- binding protein
- cell death
- cell proliferation
- physical activity
- skeletal muscle
- combination therapy
- peritoneal dialysis
- prognostic factors
- patient reported outcomes
- deep learning
- glycemic control
- data analysis
- big data
- chemotherapy induced
- patient reported