Effects of intracoronary low-dose prourokinase administration on ST-segment elevation in patients with myocardial infarction and a high thrombus burden: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of low-dose prourokinase (pro-UK) administration during primary percutaneous coronary intervention (PCI) for the treatment of acute ST-segment elevation myocardial infarction (STEMI) in patients with a high thrombus burden. METHODS: A prospective, randomized controlled trial was conducted at the Inner Mongolia People's Hospital, China. Patients with STEMI and a high thrombus burden who underwent thrombus aspiration and primary PCI were randomly allocated to pro-UK administration or control groups. The primary endpoint was corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). RESULTS: There were no significant differences in the baseline demographics or clinical characteristics of the two groups. The CTFC, tissue myocardial perfusion grade, ST-segment resolution, and myocardial blush grade of the pro-UK group were significantly better than those of the control group. In addition, after 30 days of follow-up, the pro-UK group had better cardiac function and perfusion than the control group. There were no differences in the clinical outcomes or incidence of hemorrhage. CONCLUSIONS: Intracoronary low-dose pro-UK improves myocardial perfusion and cardiac function in patients with a high thrombus burden. Major hemorrhages still occur in patients administered pro-UK, but are no more frequent.Study registration: Chinese Clinical Trial Registry (ChiCTR1900022290).

LncRNA SOX2OT facilitates LPS-induced inflammatory injury by regulating intercellular adhesion molecule 1 (ICAM1) via sponging miR-215-5p.

AIM: Long non-coding RNA SOX2 overlapping transcript (SOX2OT) is closely related to heart failure and myocardial damage. We attempted to investigate its role in endotoxin lipopolysaccharide (LPS) injury in cardiomyocytes. MATERIALS & METHODS: Cell viability, apoptosis rate, and levels of pro-inflammatory cytokines and apoptosis- and oxidative stress-related proteins were measured by MTS assay kit, flow cytometry, western blotting, and commercial kits. Physical interactions were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay. RESULTS: Silencing SOX2OT and reinforcing miRNA (miR)-215-5p protected human AC16 cardiomyocytes from LPS-induced oxidative and inflammatory injuries by inhibiting intercellular adhesion molecule 1 (ICAM1). SOX2OT directly interacted with miR-215-5p, and miR-215-5p could target ICAM1. CONCLUSION: Inhibiting SOX2OT/miR-215-5p/ICAM1 axis might be a possible approach to treat myocardial damage. LAY ABSTRACT: Lipopolysaccharide (LPS) is an endotoxin from some bacteria including Escherichia coli, and it can cause inflammation in different tissues/cells including myocardia/cardiomyocytes, resulting in diseases such as myocarditis, cardiomyopathy, and cardiac hypertrophy. The underlying mechanism was not completely clarified, but known to include the dysregulation of non-coding RNAs. Herein, we demonstrated the biological role of long non-coding RNA SOX2 overlapping transcript (SOX2OT) in LPS-infected cardiomyocytes. Eventually, we found that inhibiting the expression of SOX2OT could mitigate LPS-induced a series of injuries in human cardiomyocytes, and SOX2OT interacts with a microRNA named as miR-215-5p. Besides, restoring miR-215-5p elicited similar effects to SOX2OT knockdown. Collectively, we concluded that SOX2OT binding to miR-215-5p might protect cardiomyocytes from LPS infection through regulating an important protein named ICAM1. This study suggested SOX2OT/miR-215-5p might be novel potential treatment targets in bacterial infection-related myocardial damages.

Ferroptosis-Specific Inhibitor Ferrostatin-1 Relieves H2O2-Induced Redox Imbalance in Primary Cardiomyocytes through the Nrf2/ARE Pathway.

OBJECTIVE: Ischemic heart disease (IHD) has always been the focus of attention of many researchers in cardiovascular disease, and its pathogenesis is also very complicated. Ferroptosis may be involved in the occurrence and development of IHD. METHODS: First, primary cardiomyocytes were treated with H2O2 to simulate the IHD in vitro model. After pretreatment with different concentrations of ferrostatin-1, cell survival rate was detected by MTT method, cell apoptosis was detected by TUNEL staining and flow cytometry, and the expression of oxidative stress, ferroptosis, and related molecules of Nrf2/ARE pathway was detected by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The mortality of primary cardiomyocytes in the H2O2 group was obviously increased. Ferrostatin-1 treatment can effectively inhibit cell death, improve antioxidant enzyme activity, inhibit the expression of ferroptosis-related molecules, and activate Nrf2/ARE pathway expression. CONCLUSION: Ferroptosis-specific inhibitor ferrostatin-1 relieves H2O2-induced redox imbalance in primary cardiomyocytes through the Nrf2/ARE pathway, inhibits ferroptosis, and thereby slows cardiomyocyte death.

New Ultrasound-Controlled Paclitaxel Releasing Balloon vs. Asymmetric Drug-Eluting Stent in Primary ST-Segment Elevation Myocardial Infarction　- A Prospective Randomized Trial.

BACKGROUND: Application of drug-coated balloons (DCBs) is popular for the treatment of percutaneous coronary intervention (PCI). A new DCB has been designed as ultrasound-controlled paclitaxel releasing. This study was conducted to determine whether a DCB-only strategy has a similar safety profile and equal angiographic and clinical outcomes to DES implantation in primary ST-elevation myocardial infarction (STEMI) patients, as well as determine the efficiency and safety of this new DCB.Methods and Results:Overall, 184 pretreated STEMI patients were randomized into DCB and DES groups with a 1:1 allocation. The main study end-point was late lumen loss (LLL) during the 9 months after PCI. Late lumen loss was reported to be 0.24±0.39 mm in the DCB group and 0.31±0.38 mm in the DES group (P=0.215). Diameter stenosis was 28.27±15.35% in the DCB group and 25.73±15.41% in the DES group (P=0.312). Major adverse cardiovascular events (MACEs) were reported in 3 patients (3.4%) in the DCB group and 4 patients (4.7%) in the DES group (P=0.718). TLR and TVR in the DCB group was 2.3%, 3.4% and 2.4%, 3.5% in the DES group (P=1.000), respectively. No cardiac death and stent thrombosis (ST) was found in the DCB group at 12 months clinical follow up. CONCLUSIONS: The DCB-only strategy showed good angiographic and clinical outcomes in the 9- and 12-month follow-up periods, respectively. The VasoguardTM DCB is safe and feasible to treat STEMI patients.