Model Embraced Electromechanical Coupling Time for Estimation of Heart Failure in Patients With Hypertrophic Cardiomyopathy.

Objective: This study aimed to establish a model embraced electromechanical coupling time (EMC-T) and assess the value of the model for the prediction of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods: Data on 82 patients with HCM at Shaanxi Provincial People's Hospital between February 2019 and November 2021 were collected and then formed the training dataset (n = 82). Data were used to screen predictors of HF using univariate and multivariate analyses. Predictors were implemented to discover the optimal cut-off value, were incorporated into a model, and shown as a nomogram. The cumulative HF curve was calculated using the Kaplan-Meier method. Additionally, patients with HCM at other hospitals collected from March 2019 to March 2021 formed the validation dataset. The model's performance was confirmed both in training and validation sets. Results: During a median of 22.91 months, 19 (13.38%) patients experienced HF. Cox analysis showed that EMC-T courses in the lateral wall, myoglobin, PR interval, and left atrial volume index were independent predictors of HF in patients with HCM. Five factors were incorporated into the model and shown as a nomogram. Stratification of patients into two risk subgroups by applying risk score (<230.65, ≥230.65) allowed significant distinction between Kaplan-Meier curves for cumulative incidence of HF events. In training dataset, the model had an AUC of 0.948 (95% CI: 0.885-1.000, p < 0.001) and achieved a good C-index of 0.918 (95% CI: 0.867-0.969). In validation dataset, the model had an AUC of 0.991 (95% CI: 0.848-1.000, p < 0.001) and achieved a strong C-index of 0.941 (95% CI: 0.923-1.000). Calibration plots showed high agreement between predicted and observed outcomes in both two datasets. Conclusion: We established and validated a novel model incorporating electromechanical coupling time courses for predicting HF in patients with HCM.

Matrine pre-treatment suppresses AGEs- induced HCSMCs fibrotic responses by regulating Poldip2/mTOR pathway.

The fibrotic response of vascular smooth muscle cells (VSMCs) takes responsibilities in atherosclerosis. Advanced glycation end products (AGEs) induce and promote the fibrotic responses of VSMCs. Matrine shows potent anti-fibrotic and cardio-protective effects. This study was aimed to investigate the underlying mechanisms of matrine's inhibitory effects on AGEs-induced VSMCs fibrotic responses. Cultured human coronary smooth muscle cells (HCSMCs) were pre-treated with matrine and exposed to AGEs. Specific siRNA was used to silence polymerase delta interacting protein 2 (Poldip2) expression. Sircol collagen assay was used to assess collagen content. Protein expression and phosphorylation levels were determined by Western blotting. Matrine pre-treatment significantly reduced collagen content, increased smooth muscle myosin heavy chain 11 (MYH11) and Poldip2 expression, decreased expressions of collagen I, ß1-integrin, phsphoinositide-3-kinase (PI3K) and nuclear phosphorylated p70S6k, and reduced phosphorylation levels of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) in HCSMCs exposed to AGEs in a concentration dependent manner. Specific siRNA effectively silenced Poldip2 expression and impaired matrine's effect on collagen content, expressions of MYH11, collagen I, ß1-integrin, PI3K, nuclear p-p70S6k and phosphorylation levels of Akt and mTOR in HCSMCs exposed to AGEs. Matrine suppresses AGEs- induced fibrotic responses in HCSMCs via regulating Poldip2/mTOR signaling pathway.

Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages.

BACKGROUND The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL AND METHODS Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final concentrations of 0, 25, 50, and 100 µg/mL. Several cells were then treated with matrine at serial diluted concentrations. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining was used to evaluate reactive oxygen species (ROS) production; a colorimetric method was used to determine the cellular antioxidant capacity; production of pro-inflammatory cytokines interleukin (IL)18 and tumor necrosis factor (TNF)alpha were determined by enzyme-linked immunosorbent assay (ELISA); and immunoblot assay was used to assess the relative protein phosphorylation and expression. RESULTS ox-LDL exposure significantly elevated intracellular ROS level and supernatant IL18 and TNFalpha concentrations, but impaired total antioxidant capacity (TAC) of macrophages. The relative phosphorylations of MAPK kinase kinases (MKK)6, MKK3, and p38 mitogen-activated protein kinases (MAPK) were increased by ox-LDL exposure. The expression levels of IL18 and TNFalpha were also increased in ox-LDL-treated macrophages. The matrine treatment reduced intracellular ROS level and supernatant IL18 and TNFalpha concentrations and increased TAC in a concentration- dependent manner. The relative phosphorylations of MKK6, MKK3, and p38 MAPK were reduced after matrine administration. Moreover, the expression levels of IL18 and TNFalpha were also decreased by matrine treatment, in a concentration-dependent manner. CONCLUSIONS ox-LDL increases inflammatory response in macrophages by activating the ROS-mediated MKKs/p38 MAPK-induced inflammatory signaling pathway. Matrine suppresses ox-LDL-induced inflammatory by inhibiting the MKKs/p38 MAPK signaling pathway.