The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H₂O₂) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H₂O₂-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.

Infiltration by dendritic cells (DCs) is markedly increased in the infarcted area following myocardial infarction (MI), and DC ablation has been shown to impair angiogenesis in mice post‑MI. Exosomes (EXs) have long been known to act as messengers between cells; however, whether EXs derived from DCs can enhance myocardial angiogenesis post‑MI remains unknown. The aim of the present study was to elucidate whether EXs derived from DCs induce myocardial angiogenesis via paracrine signaling post‑MI. In vitro, suspensions of mouse bone marrow‑derived DCs (BMDCs) were incubated with the supernatant of necrotic or normal cultured HL‑1 myocardial cells (as the MI or control group, respectively) for 24 h. EXs isolated from the supernatant of BMDCs were termed DEXs, which were added to primary cultures of rat cardiac microvascular endothelial cells (CMECs), and angiogenesis was evaluated by measuring tube formation and vascular endothelial growth factor (VEGF) expression. In vivo, different groups of DEXs were injected into the infarcted myocardium of MI model mice. Then, angiogenesis was evaluated by measuring the number of vessels and the expression of VEGF and CD31 in the infarcted myocardium using immunohistochemistry. Moreover, the expression profile of microRNAs (miRNAs or miRs) in splenic DCs of MI model mice was analyzed by Affymetrix miRNA 4.0 chip assays, then certified in DEXs by reverse transcription‑quantitative PCR analysis. Finally, miRNA‑loaded DEXs were used to induce tube formation by CMECs and angiogenesis in MI model mice. It was observed that, compared with the control group, DEXs from the MI group significantly upregulated the expression of VEGF in CMECs, enhanced tube formation by CMECs, and upregulated the expression of VEGF and CD31 in the infarcted myocardium of MI model mice. miR‑494‑3p and miR‑16a‑5p, which are associated with angiogenesis, were significantly upregulated in splenic DCs of MI model mice by Affymetrix miRNA 4.0 chip assays, miR‑494‑3p was significantly upregulated and highly enriched in DEXs from the MI group compared with the control, and DEX‑miR‑494‑3p enhanced tube formation by CMECs and angiogenesis in mice post‑MI. These results suggest that miR‑494‑3p may be secreted from DCs via EXs and promotes angiogenesis post‑MI. These findings indicate a novel DEX‑based approach to the treatment of MI.

Background: Biomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality. Methods: The present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan–Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality. Results: The follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis. Conclusions: Dynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.

Amphiregulin (AREG) is a ligand of epidermal growth factor receptor and participates in the fibrosis of multiple organs. However, whether AREG can regulate hypertrophic cardiomyopathy is not well known. This research aims to explore the effect of AREG on cardiac hypertrophy, and whether the oxidative stress and apoptosis was involved in the influence of AREG on cardiac hypertrophy. Angiotensin (Ang) II induced cardiac hypertrophy in mice and neonatal rat cardiomyocytes (NRCMs) or HL-1 cells in vitro. AREG expressions raised in the heart of mice. After AREG downregulation, the increases of Ang II induced cardiac weight and cardiomyocytes area were inhibited. Down-regulation of AREG could inhibit Ang II induced the increases of atrial natriuretic peptide, brain natriuretic peptide, beta-myosin heavy chain in the heart of mice, and NRCMs and HL-1 cells. The enhancement of oxidative stress in mice heart with Ang II treatment was alleviated by AREG knockdown. The raises of Ang II induced Bax and cleaved caspase3 in mice heart were inhibited by AREG downregulation. AREG downregulation reduced myocardial hypertrophy via inhibition of oxidative and apoptosis. AREG may be a target for future cardiac hypertrophy treatment.

Background: The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. Endothelial Foxp1 (forkhead box P1) has been shown to control endothelial cell (EC) proliferation and migration in vitro. However, whether EC‐Foxp1 participates in neointimal formation in vivo is not clear. Our study aimed to investigate the roles and mechanisms of EC‐Foxp1 in neointimal hyperplasia. Methods and Results: The wire injury femoral artery neointimal hyperplasia model was performed in Foxp1 EC‐specific loss‐of‐function and gain‐of‐function mice. EC‐Foxp1 deletion mice displayed the increased neointimal formation through elevation of vascular smooth muscle cell proliferation and migration, and the reduction of EC proliferation hence reendothelialization after injury. In contrast, EC‐Foxp1 overexpression inhibited the neointimal formation. EC‐Foxp1 paracrine regulated vascular smooth muscle cell proliferation and migration via targeting matrix metalloproteinase‐9. Also, EC‐Foxp1 deletion impaired EC repair through reduction of EC proliferation via increasing cyclin dependent kinase inhibitor 1B expression. Delivery of cyclin dependent kinase inhibitor 1B‐siRNA to ECs using RGD (Arg‐Gly‐Asp)‐peptide magnetic nanoparticle normalized the EC‐Foxp1 deletion‐mediated impaired EC repair and attenuated the neointimal formation. EC‐Foxp1 regulates matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B signaling pathway to control injury induced neointimal formation. Conclusions: Our study reveals that targeting EC‐Foxp1‐matrix metalloproteinase‐9/cyclin dependent kinase inhibitor 1B pathway might provide future novel therapeutic interventions for restenosis.