Forsythoside B Mitigates Monocrotaline-Induced Pulmonary Arterial Hypertension via Blocking the NF-κB Signaling Pathway to Attenuate Vascular Remodeling.

Purpose: Pulmonary arterial hypertension (PAH) is a devastating disease with little effective treatment. The proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by the nuclear factor-κB (NF-κB) signaling activation plays a pivotal role in the pathogenesis of PAH. Forsythoside B (FTS•B) possesses inhibitory effect on NF-κB signaling pathway. The present study aims to explore the effects and mechanisms of FTS•B in PAH. Methods: Sprague-Dawley rats received monocrotaline (MCT) intraperitoneal injection to establish PAH model, and FTS•B was co-treated after MCT injection. Right ventricular hypertrophy and pulmonary artery pressure were measured by echocardiography and right heart catheterization, respectively. Histological alterations were detected by H&E staining and immunohistochemistry. FTS•B's role in PASMC proliferation and migration were evaluated by CCK-8 and wound healing assay. To investigate the underlying mechanisms, Western blotting, immunofluorescence staining and ELISA were conducted. The NF-κB activator PMA was used to investigate the role of NF-κB in FTS•B's protective effects against PAH. Results: FTS•B markedly alleviated MCT-induced vascular remodeling and pulmonary artery pressure, and improved right ventricular hypertrophy and survival. FTS•B also reversed PDGF-BB-induced PASMC proliferation and migration, decreased PCNA and CyclinD1 expression in vitro. The elevated levels of IL-1ß and IL-6 caused by MCT were decreased by FTS•B. Mechanistically, MCT-triggered phosphorylation of p65, IκBα, IKKα and IKKß was blunted by FTS•B. FTS•B also reversed MCT-induced nuclear translocation of p65. However, all these protective effects were blocked by PMA-mediated NF-κB activation. Conclusion: FTS•B effectively attenuates PAH by suppressing the NF-κB signaling pathway to attenuate vascular remodeling. FTS•B might be a promising drug candidate with clinical translational potential for the treatment of PAH.

Impact of pre-procedural diastolic blood pressure on major adverse cardiovascular events in non ST-segment elevation myocardial infarction patients following revascularization.

Previous reports have observed a consistent J-shaped relationship between cardiac events and diastolic blood pressure (DBP). However, the EPHESUS study clearly showed that myocardial reperfusion abolished the J-shaped association, suggesting a different association pattern after revascularization. Therefore, in this study, we investigated the different patterns in which DBP affects cardiovascular risk in non ST-segment elevation myocardial infarction (NSTEMI) patients after revascularization, which may benefit the risk stratification for NSTEMI patients. We obtained the NSTEMI database from the Dryad data repository and analyzed the association between preprocedural DBP and long-term major adverse cardiovascular events (MACEs) in 1486 patients with NSTEMI following percutaneous coronary intervention (PCI). Multivariate regression models were used to assess the impact of DBP on outcomes in an adjusted fashion according to DBP tertiles. The p value for the trend was calculated using linear regression. When examined as a continuous variable, a multivariate regression analysis was repeated. Pattern stability was verified by interaction and stratified analyses. The median (interquartile range) age of the patients was 61.00 (53.00-68.00) years, and 63.32% were male. Cardiac death showed a graded increase as the DBP tertile increased (p for trend = 0.0369). When examined as a continuous variable, a 1 mmHg increase in DBP level was associated with an 18% higher risk of long-term cardiac death (95% CI: 1.01-1.36, p = 0.0311) and a 2% higher risk of long-term all-cause death (95% CI: 1.01-1.04; p = 0.0178). The association pattern remained stable when stratified by sex, age, diabetes, hypertension, and smoking status. An association between low DBP and higher cardiovascular risk was not observed in our study. We showed that higher preprocedural DBP increased the risk of long-term cardiac death and all-cause death in patients with NSTEMI following PCI.