Tanyu Tongzhi formula attenuates atherosclerotic plaque vulnerability by inhibiting CD40+ monocyte differentiation.

Background: Atherosclerosis (AS) is a chronic progressive inflammatory disease, and plaque stability plays a critical role in preventing acute events. Tanyu Tongzhi formula (TTF), a traditional Chinese medicine, has potential therapeutic effects on AS. Methods: We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40+ monocyte differentiation. AS plaque area, collagen content, and lipid area were assessed using histological staining. AS plaque-related biomarkers (monocyte chemoattractant protein 1 (MCP-1), monocyte plus macrophage (MOMA-2), von Willebrand factor (vWF), CD31, and alpha-smooth muscle actin (a-SMA)) were detected using immunohistochemistry. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. CD40 mRNA expression was detected by real-time quantitative PCR. CD40+ monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/- mice and peripheral blood mononuclear cells (PBMCs). AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting. Results: TTF treatment reduced AS plaque area, collagen content, and lipid area in AS model mice. Levels of MCP-1, MOMA-2, vWF, and CD31 were decreased, while a-SMA level was increased by TTF in model mice. TTF reduced inflammatory cytokines levels, including tumor necrosis factor receptor-a (TNF-a), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). TTF inhibited CD40+ monocyte differentiation and decreased the number of CD40+/CD40- and Ly6C+/Ly6C- cells and M1/M2 ratio in AS model mice and human PBMCs. Additionally, TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs. Conclusion: TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40+ monocyte differentiation, possibly through the regulation of the AMPK/NF-κB signaling pathway. These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS. [ABSTRACT FROM AUTHOR]