Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy.

Pathological cardiac hypertrophy induced by angiotensin II (AngII) can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots of Nardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on AngII-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosinone (25, 50, 100, and 200 µmol/L) or AngII (1 µmol/L). Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by AngII. The mRNA expression of ANP, BNP and ß-MHC was obviously elevated in AngII-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100 µmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang II-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

The value of serum metabolomics analysis in predicting the response to cardiac resynchronization therapy.

OBJECTIVE: To construct a prediction model based on metabolic profiling for predicting the response to cardiac resynchronization therapy (CRT). METHODS: Peripheral venous (PV) and coronary sinus (CS) blood samples were collected from 25 patients with heart failure (HF) at the time of CRT implantation, and PV blood samples were obtained from ten healthy controls. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). As per the clinical and echocardiographic assessment at the 6-month follow-up, the HF patients were categorized as CRT responders and non-responders. RESULTS: HF patients had altered serum metabolomic profiles that were significantly different from those of the healthy controls. Differential metabolites were also observed between CRT responders and non-responders. A prediction model for CRT response (CRT-Re) was constructed using the concentration levels of the differential metabolites, L-arginine and taurine. The optimal cutoff value of the CRT-Re model was found to be 0.343 by ROC analysis (sensitivity, 88.2%; specificity, 87.5%; Area under curve (AUC) = 0.897, P = 0.002). The concentration levels of the differential metabolites, L-arginine and lysyl-gamma-glutamate, in PV serum were significantly correlated with that in CS serum (r = 0.945 and 0.680, respectively, all P < 0.001). CONCLUSIONS: Our results suggest that serum-based metabolic profiling may be a potential complementary screening tool for predicting the outcome of CRT.