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.

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.