No abstract

Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/β-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.

Heart failure (HF) is one of the most common causes of hospital admission and readmission in patients over 65 years of age. It is a clinical syndrome resulting from structural and functional cardiac disorders that impair the heart's ability to fill with (diastolic) and/or to eject (systolic) blood commensurate with the metabolic needs of the body. 1-3 A common precursor and contributor to HF is cardiac hypertrophy, a pathological condition that sets in as the heart attempts to compensate for its poor ability to circulate the blood. Cardiac hypertrophy is characterized by an increase in the size of individual cardiomyocytes, rather than their overall numbers, in order to temporarily maintain the cardiac output. 4 Long-term hypertrophy eventually leads to ischaemia, arrhythmia, heart failure and sudden death. 5 However, the precise pathophysiological mechanisms that explain the transition from hypertrophy to clinical HF are not well understood. 6

Background: The core pathophysiological process of myocardial ischemia reperfusion injury (MIRI) is the excessive reactive oxygen species (ROS) production (including •O2-, H2O2, •OH) in the injured areas. Manganese tetroxide (Mn3O4) nanozymes are capable of scavenging multiple ROS, but whether they are applicable in MIRI is unclear. Rat IgG-modified liposomes can be specifically phagocytosed by activated neutrophils. Activated neutrophils can penetrate the vascular barrier and infiltrate into the inflamed myocardial tissue induced by MIRI. We synthesized IgG-Lip-Mn3O4 (rat IgG-modified liposomes encapsulated with Mn3O4 nanozyme). It is unclear whether they can be phagocytosed by activated neutrophils and then infiltrate into deep myocardial tissues to remove excess ROS. Methods: Fluorescent probe technique was used to test ROS scavenging ability of IgG-Lip-Mn3O4. Apoptosis and cell death were detected with regular staining kits. Flow cytometry and in vivo imaging system were used to evaluate the targeting ability of IgG-Lip-Mn3O4 on myocardial tissue. Serum inflammatory factors were measured with ELISA kits. Echocardiography was used to detected cardiac function. Pathological staining was used to detected scar size, cardiac fibrosis, and cardiac remodeling. Immunofluorescence was used to detect vascular regeneration and macrophage polarization. Results: Mn3O4 nanozyme can scavenge various ROS such as •O2-, •OH and exert therapeutic effects in MIRI. IgG-Lip-Mn3O4, specifically phagocytosed by activated neutrophils, can be carried to the deep injured areas by utilizing the chemotactic effect of activated neutrophils towards inflammation areas. IgG-Lip-Mn3O4 could remove excess ROS from the injured areas, reduce the release of inflammatory factors and increase the content of M2-phenotype macrophages. It also protected cardiomyocytes against apoptosis and decreased the infarction size. IgG-Lip-Mn3O4 not only decreased scar tissue accumulation and ventricular remodeling, but also promoted angiogenesis and restored cardiac function. In addition, IgG-Lip-Mn3O4 was biocompatible and did not cause organ toxicity. Conclusions: IgG-Lip-Mn3O4 can specifically reach the injured areas and remove a variety of ROS. By reducing inflammatory responses and apoptosis, IgG-Lip-Mn3O4 provided precise and effective treatment for MIRI.

Background and objectives: In clinical practice, we observed that the prognoses of patients with heart failure and atrial fibrillation were worse than those of patients with only heart failure or atrial fibrillation. The study aims to get a better understanding of the common pathogenesis of the two diseases and find new therapeutic targets. Materials and Methods: We downloaded heart failure datasets and atrial fibrillation datasets from the gene expression omnibus database. The common DEGs (differentially expressed genes) in heart failure and atrial fibrillation were identified by a series of bioinformatics methods. To better understand the functions and possible pathways of DEGs, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We identified 22 up-regulated genes and 14 down-regulated genes in two datasets of heart failure and 475 up-regulated and 110 down-regulated genes in atrial fibrillation datasets. In addition, two co-upregulated (FRZB, SFRP4) and three co-downregulated genes (ENTPPL, AQP4, C1orf105) were identified. GO enrichment results showed that these common differentially expressed genes were mainly concentrated in the signal regulation of the Wnt pathway. Conclusions: We found five crucial genes in heart failure and atrial fibrillation, which may be potential therapeutic targets for patients with heart failure and atrial fibrillation.