Effect of sacubitril-valsartan on left ventricular remodeling and NT-proBNP in patients with heart failure complicated with hypertension and reduced ejection fraction.

OBJECTIVE: To analyze the effect of sacubitril-valsartan on left ventricular remodeling and NT-proBNP in heart failure patients with hypertension and reduced ejection fraction. METHOD: A retrospective analysis was conducted on 112 heart failure patients with reduced ejection fraction (HFrEF) and concomitant hypertension who were treated in Baoji Central Hospital from May 2019 to October 2021. Standard heart failure treatment was applied in both groups. Besides, the observation group (n=60) was additionally treated with sacubitril/valsartan (initial dose of 50 mg twice daily, adjusted every 2-4 weeks by doubling the dose to a maximum of 200 mg twice daily based on the patients' actual conditions and tolerance), and the control group (n=52) received valsartan (80 mg once daily). The treatment duration for both groups was 6 months. Therapeutic efficacy, blood pressure, echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left ventricular remodeling before and after treatment were recorded and compared between the two groups, as well as the adverse drug reactions during the treatment and life quality after treatment. Finally, multifactor regression analysis was performed to screen the independent risk factors affecting patient prognosis. RESULTS: Compared with the CG, the overall response rate in the OG was evidently higher (P < 0.001); the improvements in blood pressure, NT-proBNP, interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular mass index (LVMI) were more significant in the OG (all P < 0.001). Both groups showed marked improvements in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and (left ventricular end-systolic diameter) LVESD compared to baseline, with more significant improvement in the OG compared with the CG (all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups. However, post-treatment quality of life was much higher in the OG compared to the CG (P < 0.001). Comorbid diabetes and treatment regimen were identified as independent risk factors affecting patient prognosis. CONCLUSION: Sacubitril-valsartan can effectively improve blood pressure, cardiac function and ventricular remodeling in patients with HFrEF and hypertension without increasing adverse reactions. It is highly safe and worthy of clinical promotion.

RNA binding Motif protein-38 regulates myocardial hypertrophy in LXR-α-dependent lipogenesis pathway.

Myocardial hypertrophy is a pathological thickening of the myocardium, leading to various ailments, such as myocardial infarction and heart failure. RBM38 is critical in modulating mRNA translation for multiple protective activities such as p53 tumor repressor and p21 kinase cell cycle inhibitors. Liver X receptors (LXR-α) agonists reduce cellular hypertrophy initiated by various hypertrophic stimuli as lipopolysaccharides and Ang II. This research investigates the possible cooperation between RBM38 and LXR-α and mechanisms in modulating myocardial hypertrophy. H9C2 cells were treated with PE, TNF-α, and AngII to induce myocardial hypertrophy. RBM38 and LXR- α were overexpressed or silenced in H9C2 cells, and hypertrophy markers (ANF and Myh7) were determined with Western blot and RT-qPCR. Binding assays were done through RNA immunoprecipitation. H&E and Rhodamine-labeled phalloidin staining assays were used to assess the relative cell surface change. The results demonstrated RBM38 downregulation in in vitro models of myocardial hypertrophy. Modulation of RBM38 expression also exerted inverse effects on myocardial hypertrophy markers. Further observations also showed that LXR-α expression regulates the myocardial hypertrophy markers in H9C2 cells and RBM38 binds with LXR-α mRNA, consequently inhibiting LXR-α expression. Finally, overexpression of RBM38 rescues Angiotensin II-induced myocardial hypertrophy by regulating LXR-α dependent lipogenesis pathway. In conclusion, RBM38 Overexpression rescues Angiotensin II-induced myocardial hypertrophy by regulating LXR-α dependent lipogenesis pathway.

Obeticholic acid protects against diabetic cardiomyopathy by activation of FXR/Nrf2 signaling in db/db mice.

Diabetic cardiomyopathy (DCM) is one of the major cardiac complications in diabetic patients and a major reason for the death of diabetic patients. Obeticholic acid (OCA) is a semi-synthetic bile acid analogue. The objective of the present study was to investigate the possible cardio-protective effect of OCA against DCM. db/db diabetic mice were given OCA with or without injection of LV-short hairpin farnesoid X receptor (shFXR), and general glucose and lipid metabolism, myocardial morphology and function, myocardial fibrosis, inflammation and oxidative stress were evaluated. We found that OCA significantly ameliorated metabolic dysfunctions. Moreover, OCA attenuated morphological injury of cardiac tissue, restored the abnormal changes of hemodynamic variables and echocardiographic parameters. The Sirius-Red staining of cardiac tissue and mRNA expression of fibrotic biomarkers, including connective tissue growth factor, osteopontin, Transforming growth factor-ß1, atrial natriuretic peptide, Collagen Ⅰ, and Collagen Ⅲ were decreased by OCA. Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were reduced by OCA. Moreover, OCA decreased oxidant products and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and the expression and activities of antioxidant enzymes. Injection of LV-shFXR downregulated FXR expression and inhibited all these beneficial effects of OCA. FXR is major target that mediated that beneficial effect of OCA. In summary, FXR/Nrf2 signaling was involved in OCA-induced amelioration of metabolic disorder, oxidative stress, inflammation, fibrosis and myocardial dysfunction. Our findings provide new evidence for the interaction of FXR and Nrf2 signaling and novel option for the intervention of DCM.