Oxidized low-density lipoprotein induces M2-type differentiation of macrophages to promote the protracted progression of atherosclerotic inflammation in high-fat diet-fed ApoE -/- mice.

In this study, the significance of oxidized low-density lipoprotein (ox-LDL) in promoting the progression of atherosclerosis was investigated by inducing the differentiation of macrophages into the M2 subtype within a high-fat diet-induced ApoE -/- mouse model. The study also evaluated the effects of ß2-AR agonists and blockers on this process. Ox-LDL was found to have significantly promoted the differentiation of macrophages into the M2 type and induced related functional alterations. Furthermore, it activated the pyroptosis pathway and encouraged the release of lactate dehydrogenase. The administration of ß2-AR agonists intensified these processes, while ß2-AR blockers had the opposite effect. In animal experiments, the model group displayed elevated numbers of M2-type macrophages beneath the aortic root intima, an increased rate of plaque destruction, and the formation of atherosclerotic plaques compared to the control group. The SAL (Salbutamol) group exhibited even more severe plaque development than the model group. Conversely, the ICI (ICI118551) group demonstrated M2-type macrophage levels comparable to the control group, with a higher plaque destruction rate than controls but significantly lower than the model group, and no atherosclerotic plaques. These findings suggest that ox-LDL promoted the differentiation of recruited monocytes into M2-type macrophages, leading to a shift in the inflammatory response from M1 to M2 macrophages. This alteration resulted in the persistence of atherosclerotic inflammation, as M2-type macrophages were prone to cell membrane rupture (such as pyroptosis), contributing to the continuous recruitment of circulating monocytes and heightened inflammatory reactions within atherosclerotic plaques. Consequently, this process fueled the progression of atherosclerosis.

MiR-181b suppresses angiogenesis by directly targeting cellular communication network factor 1.

Angiogenesis is essential for various physiological and pathological processes. Previous studies have shown that miRNAs play an important role in blood vessel development and angiogenesis. Recent studies have suggested that miR-181b might be involved in the regulation of angiogenesis in tumors. However, whether miR-181b plays a role in angiogenesis in nontumor diseases is unclear. We found that miR-181b expression was downregulated in hypoxia-stimulated primary human umbilical vein endothelial cells (HUVECs) and a mouse hindlimb ischemia (HLI) model. Gain- and loss-of-function studies showed that a miR-181b mimic inhibited HUVEC migration and tube formation in vitro, and a miR-181b inhibitor had the opposite effects. In vivo, agomir-181b suppressed perfusion recovery in the HLI model and capillary density in a Matrigel plug assay, while perfusion recovery and capillary density were increased by injection of antagomir-181b. Mechanistically, we showed with a reporter assay that cellular communication network factor 1 (CCN1) was a direct target of miR-181b. Moreover, miR-181b suppressed angiogenesis at least in part by targeting CCN1 to inhibit the AMPK signaling pathway. Our research suggests that miR-181b suppresses angiogenesis by directly targeting CCN1, which provides new clues for pro-angiogenic treatment strategies.

Inhibition of differentiation of monocyte-derived macrophages toward an M2-Like phenotype May Be a neglected mechanism of ß-AR receptor blocker therapy for atherosclerosis.

The clinical efficacy of adrenergic ß-receptor (ß-AR) blockers in significantly stabilizing atherosclerotic plaques has been extensively supported by evidence-based medical research; however, the underlying mechanism remains unclear. Recent findings have highlighted the impact of lipid-induced aberrant polarization of macrophages during normal inflammatory-repair and regenerative processes on atherosclerosis formation and progression. In this review, we explore the relationship between macrophage polarization and atherosclerosis, as well as the influence of ß-AR blockers on macrophage polarization. Based on the robust evidence supporting the use of ß-AR blockers for treating atherosclerosis, we propose that their main mechanism involves inhibiting monocyte-derived macrophage differentiation towards an M2-like phenotype.

The balance between CD4+ T helper 17 and T-cell immunoglobulin and mucin domain 3 is involved in the pathogenesis and development of atrial fibrillation.

Background: To investigate the expression of Th17, T lymphocyte immunoglobulin mucin 3 (TIM-3+) cells and their related cytokines in atrial fibrillation (AF) and their clinical significance. Methodology: A total of 90 patients with AF were divided into paroxysmal group (n=45) and chronic group (n=45), and 45 healthy volunteers were selected as the control group. The proportion of Th17 cells and Tim-3 + cells in the peripheral blood were detected. The concentrations of related cytokines in peripheral blood serum were determined. The correlation between Th17 / Tim-3+ cells and related cytokines was analysed. Results: Compared with the control group, the proportion of Th17 cells and the concentration of related cytokines (IL-17, IL-6 and Matrix metalloproteinase (MMP9)) in peripheral blood of patients with paroxysmal and chronic AF increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Compared with the paroxysmal group, the proportion of Th17 cells and the concentration of related cytokines in the peripheral blood of patients in the chronic group increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Conclusion: Th17 / Tim-3 + cell balance is involved in AF, and can be used as a target for AF treatment.