Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Nadir oxygen delivery during cardiopulmonary bypass in acute type A aortic dissection repair.

Background: Acute type A aortic dissection (ATAAD) is associated with high mortality. Previous studies found that maintaining a high level of oxygen delivery (DO2) could decrease the postoperative mortality, but the minimum threshold of DO2 remained unclear. The present study aimed to investigate the relationship between maintaining intraoperative DO2 ≥280 mL/(min·m2) and the 90-day postoperative mortality of ATAAD patients. Methods: The clinical data of 178 ATAAD patients who underwent Sun's procedure in our center from January 2018 to July 2022 were retrospectively analyzed in the present cohort study. The included patients were divided into hypoxic group [DO2 <280 mL/(min·m2)] and normoxic group [DO2 ≥280 mL/(min·m2)]. The primary endpoint was the 90-day all-cause mortality, and the secondary endpoints were postoperative mechanical ventilation time, the application of continuous renal replacement therapy (CRRT), brain complications, and other postoperative complications. Results: Among all the patients, a total of 23 patients died 90 days postoperatively. Compared with the hypoxic group, blood flow, hematocrit (HCT), DO2, and DO2/VO2 ratio during cardiopulmonary bypass (CPB) were significantly higher, while the need for CRRT and the 90-day mortality were significantly lower in the normoxic group. The median follow-up time was 4 months. Kaplan-Meier curve indicated that the survival rate of ATAAD patients in the normoxic group was significantly higher. Univariate cox regression analysis demonstrated that 90-day mortality was reduced by 72.1% in the normoxic group. Conclusions: Maintaining DO2 ≥280 mL/(min·m2) during CPB by increasing CPB flow and HCT level is associated with decreased 90-day mortality of ATAAD patients.

The application of del Nido cardioplegia for myocardial protection in adult coronary artery bypass grafting: a cohort study.

BACKGROUND: Del Nido cardioplegia is widely used in adult cardiopulmonary bypass surgery and has a satisfying cardioprotective effect for about 90 minutes by single dose, but the effect in patients with coronary heart disease remains confused. The purpose of this study was to examine the cardioprotective effect of del Nido cardioplegia in adult multivessel coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: This retrospective comparative analysis included 124 consecutive patients undergoing isolated on-pump CABG performed by a single surgeon between January 2017 and December 2020. The demographic characteristics and medical history of the included patients were collected. The included patients were divided into two groups: a del Nido cardioplegia (DN) group and a conventional multidose blood cardioplegia (BC) group. Perioperative, intraoperative, and postoperative indicators and complications were compared. RESULTS: Compared with the BC group, CPB and aortic cross-clamp time were significantly shorter in the DN group. In the early postoperative period, the hemoglobin concentration in the DN group was significantly higher than that in the BC group (P<0.05). CONCLUSIONS: This study demonstrated that the application of del Nido cardioplegia in adult on-pump CABG could lead to a significantly shorter aortic cross-clamp and CPB time, as well as a higher hemoglobin concentration in the early postoperative period. The myocardial protective effect of del Nido cardioplegia is not inferior to that of conventional blood perfusion in adult on-pump CABG.

Cracking to curling transition in drying colloidal films.

Drying-induced cracking is widely encountered in nature and is of fundamental interest in industrial applications. During desiccation, the evolution of water content is nonlinear. Considering the inhomogeneous procedure of desiccation, it is worth considering whether water content will affect the crack pattern formation. To address this concern, in this paper, we report an experimental investigation on the effect of water content on the failure mode in drying colloidal films. A distinct failure transition from random cracking to curling is found when the initial water content increases gradually. When the water content is below a critical value for given film thickness, random desiccation cracking driven by shrinkage is observed. Beyond this critical water content, the film curls with the advent of several main cracks. It is also found that the critical water content corresponding to the transition point depends on the film thickness. In order to qualitatively interpret the experimental observation, a theoretical model is established by adopting the fracture mechanics based on the energy method. The model is found to agree well with the experimental results, elucidating the effects of initial water content on the crack patterns and the transition of failure modes.