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.

[Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for Stanford type A aortic dissection: analysis of 23 cases].

OBJECTIVE: To assess the clinical outcomes of brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for treatment of Stanford type A aortic dissection. METHODS: Twenty-three patients with Stanford type A aortic dissection requiring arch replacement underwent brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique. The operations were performed within 72 h (20 cases) or 3-14 days (3 cases) after the onset of aortic dissection. RESULTS: There was no perioperative death in these cases. The mean extracorporeal circulation time was 209∓52 min, the aortic cross clamp time was 85∓21 min, and the mean chest tube output within the first 24 h after the operation was 570∓263 mL; none of the patients required chest reopening for management of bleeding. Postoperative acute renal failure requiring hemodialysis occurred in 3 cases, transient neurologic dysfunction in 2 cases, paraplegia in case and hematosepsis in 1 case. No such complications as permanent neurologic deficit or postoperative visceral malperfusion occurred in these cases. All the patients survived and were discharged from hospital without experiencing severe complications in the follow-up for 6-18 months. CONCLUSION: Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique is a safe and simple procedure with controllable bleeding and can serve as an optional procedure for aortic arch replacement.

Advanced oxidation protein products in predicting acute kidney injury following cardiac surgery.

To test the hypothesis whether serum advanced oxidation protein products (AOPP) are associated with increased acute kidney injury (AKI) after cardiopulmonary bypass (CPB) and could serve as a biomarker in this aspect, we performed a prospective cohort study. Thirty-five (22.3%) patients developed AKI, and 32 age- and gender-matched patients without AKI were selected as control. Serum AOPP 1 h after CPB were significantly higher among AKI patients compared with non-AKI patients (81.8 ± 18.6 versus 67.4 ± 12.5 µmol/L, p < 0.001), with an area under the receiver-operating characteristic (ROC) curve of 0.714. An optimal serum AOPP 1 h after CPB cutoff of 69.9 µmol/L had a sensitivity of 74%, specificity of 63% and a positive predictive value of 68% for predicting AKI. These results demonstrated that serum AOPP might be an early biomarker for AKI after CPB.

Serum salusin-α levels are inversely correlated with the presence and severity of coronary artery disease.

We sought to measure serum salusin-α levels in patients with coronary artery disease (CAD) and to assess their correlation with the severity of the disease. We enrolled 172 patients with CAD and 91 controls. We assessed the angiographic severity of CAD by coronary atherosclerosis index (CAI) and detected serum salusin-α levels by enzyme-linked immunosorbent assay (ELISA). We demonstrated that CAD patients had significantly lower serum salusin-α levels compared to controls. Moreover, serum salusin-α levels were independently and negatively correlated with the presence and severity of CAD. These findings indicated that salusin-α might serve as a potential biomarker for predicting the development and progression of CAD.