Objective— Smooth muscle cells (SMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute at least 50% of atheroma foam cells. In mice, SMCs contribute fewer total lesional cells. The purpose of this study was to determine the contribution of SMCs to total foam cells in apolipoprotein E-deficient (ApoE −/− ) mice, and the utility of these mice to model human SMC foam cell biology and interventions. Approach and Results— Using flow cytometry, foam cells in the aortic arch of ApoE −/− mice were characterized based on the expression of leukocyte-specific markers. Nonleukocyte foam cells increased from 37% of total foam cells in 27-week-old to 75% in 57-week-old male ApoE −/− mice fed a chow diet and were ≈70% in male and female ApoE −/− mice following 6 weeks of Western diet feeding. A similar contribution to total foam cells by SMCs was found using SMC-lineage tracing ApoE −/− mice fed the Western diet for 6 or 12 weeks. Nonleukocyte foam cells contributed a similar percentage of total atheroma cholesterol and exhibited lower expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1) when compared with leukocyte-derived foam cells. Conclusions— Consistent with previous studies of human atheromas, we present evidence that SMCs contribute the majority of atheroma foam cells in ApoE −/− mice fed a Western diet and a chow diet for longer periods. Reduced expression of ABCA1, also seen in human intimal SMCs, suggests a common mechanism for formation of SMC foam cells across species, and represents a novel target to enhance atherosclerosis regression.

Atherosclerosis is the process underlying heart attack and stroke. A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core. Pro-phagocytic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Background Explore markers to predict the clinical outcomes of checkpoint inhibitors have high unmet needs. The following study investigates whether hematologic parameter such as systemic immune‐inflammation index (SII), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) is associated with nivolumab efficacy in advanced non‐small‐cell lung cancer (NSCLC). Methods Advanced/metastatic NSCLC patients treated with nivolumab monotherapy for second‐line or further‐line treatment at Jilin Cancer Hospital between March 2016 and July 2018 were enrolled in this retrospective study. The optimal cutoff values of SII, NLR, and PLR for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve. Progression‐free survival (PFS) and overall survival (OS) were calculated and compared using Kaplan‐Meier method and log‐rank test. Prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses. Results A total of 44 patients with advanced NSCLC were included; the median age was 60 (range: 43‐74). The optimal cutoff value of SII/NLR/PLR predicted PFS and OS was 603.5, 3.07, and 144. Low SII, NLR, and PLR were associated with longer PFS (HR for SII = 0.34, 95%CI 0.15‐0.76, P = 0.006; HR for NLR = 0.46, 95%CI 0.22‐0.99, P = 0.048; HR for PLR = 0.39, 95%CI 0.17‐0.94, P = 0.025) and OS (HR for SII = 0.16, 95%CI 0.05‐0.51, P = 0.005; HR for NLR = 0.20, 95%CI 0.06‐0.62, P = 0.002; HR for PLR = 0.20, 95%CI 0.06‐0.73, P = 0.008). NLR ≤ 3.07, PLR ≤ 144, SII ≤ 603.5 were independently associated with longer PFS and OS. Conclusion The SII, NLR, and PLR are promising prognostic predictor for patients with metastatic NSCLC patients.