Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms. THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of various proteins were tested using the CCK8 kit, Oil Red O staining, flow cytometry, and western blotting, respectively. Ox-LDL treatment alone promoted macrophage-derived foam cell formation, while salidroside treatment alone inhibited it (p < 0.05). The number of early/late apoptotic cells decreased with salidroside treatment in a dose-dependent manner (p < 0.05). Salidroside dramatically upregulated nuclear factor erythroid 2-related factor 2, but had no effect on heme oxygenase-1 expression; moreover, it markedly downregulated ox-LDL receptor 1 and upregulated ATP-binding cassette transporter A1. Salidroside also obviously decreased the phosphorylation of JNK, ERK, p38 MAPK, and increased that of Akt. However, the total expression of these proteins was not affected. Based on our findings, we speculate that salidroside can suppress ox-LDL-induced THP1-derived foam cell formation and apoptosis, partly by regulating the MAPK and Akt signaling pathways.

Background: Hypertriglyceridemia (HTG) increases the risk for atherosclerotic cardiovascular disease, but underlying mechanisms are incompletely understood. Circulating monocytes play an important role in atherogenesis by infiltrating arterial walls, where they differentiate into macrophages. We tested the hypothesis that HTG is mechanistically linked to atherogenesis by altering the monocyte phenotype and infiltration into atherosclerotic lesions in a model of diet-induced atherogenesis in Ldlr^−/− mice. Methods: HTG was induced in male Ldlr^−/− mice, fed a Western, high-fat high-cholesterol diet, by daily injection of poloxamer 407 (P407), a lipoprotein lipase inhibitor, for seven weeks. Atherosclerosis, monocyte phenotypes, and monocyte migration into atherosclerotic lesions were determined by well-validated methods. Results: Compared with the saline control, P407 injection in Ldlr^−/− mice rapidly induced profound and persistent HTG, modestly elevated plasma cholesterol levels, and increased levels of triglyceride and cholesterol carried in very-low-density lipoprotein and low-density lipoprotein. Unexpectedly, mice receiving P407 versus saline control showed less atherosclerosis. Following induction of HTG by P407, CD36⁺ (also CD11c⁺), but not CD36⁻ (CD11c⁻), monocytes showed early increases in lipid accumulation, but the number of CD36⁺ (not CD36⁻) monocytes was dramatically decreased afterwards in the circulation until the end of the test. Concurrently, CD36⁺ (CD11c⁺) monocyte migration into atherosclerotic lesions was also reduced in mice receiving P407 versus controls. Conclusions: P407 induced severe HTG, but reduced atherosclerosis, in Ldlr^−/− mice, possibly because of profound reductions of circulating CD36⁺ (CD11c⁺) monocytes, leading to decreased monocyte migration into atherosclerotic lesions.

Background Mesenchymal stem cells (MSCs), a type of seed cell, are expected to improve impaired diabetic cardiac function. Inflammation and autophagy play an important role in the development of metabolic disorder-induced heart failure. The aim of this work was to assess the effect of adipose-derived mesenchymal stem cells (ADMSCs) on metabolic disorder-induced heart failure and the underlying mechanisms. Methods Eight weeks old male C57BL/6 mice were randomly divided into three groups: normal chow mice (NC group), high-fat diet-fed and streptozotocin-treated mice (HFD+STZ group) and mice administered with ADMSCs-once per week for 3 months after the mice were treated with HFD+STZ (ADMSCs+HFD+STZ group). Once a week lipid and glucose levels were measured and echocardiography was performed. Immunohistochemistry was used to detect the adhesion of macrophages in heart tissue in all three groups. Inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-8 (CXCL-15) were measured by western blot or RT-qPCR. In vitro, H9c2 cardiomyocytes were stimulated by 33mM glucose in the presence or absence of IL-1β. Transmission electron microscopy, mRFG-GFP-LC3 assays and flow cytometry were used to investigate autophagy-related apoptosis in H9c2 cells. Results HFD+STZ treated mice presented significant cardiac hypertrophy, body weight loss, hyperglycemia and hyperlipidemia. However, these changes were remarkably reversed by the administration of ADMSCs. The administration of ADMSCs also remits histological alterations and deposition of collagen in the heart tissue. Furthermore, ADMSCs downregulated the adhesion of macrophages in heart tissue. More importantly, IL-1β from macrophages increased the autophagy of myocardial cells stimulated with high glucose, which eventually led to apoptosis and cardiac dysfunction. Conclusions This study confirmed that ADMSCs may have potential for use in improving cardiac function by restraining autophagy and apoptosis of myocardial cells. We also identified the roles of the IL-1β in hyperglycemia- and hyperlipidemia-induced cardiac injuries, which may be a key factor for diabetic complications.