Jianpi Qutan Formula attenuates vulnerable plaques by regulating IGFBP3

Spleen deficiency phlegm-turbidity syndrome (SD-PTS) is a common traditional Chinese medicine (TCM) pattern in unstable angina (UAP). Its core pathogenesis involves the spleen failing in its transportation and transformation functions, leading to the generation of phlegm-turbidity that obstructs the vessels. Jianpi Qutan Formula (JPQT) is a TCM compound formulated based on the therapeutic principles of "strengthening the spleen, resolving phlegm, and activating blood." It has been clinically used for the long-term treatment of patients with coronary heart disease, effectively alleviating angina symptoms and regulating lipid metabolism. However, the molecular mechanism by which JPQT stabilizes vulnerable plaques remains to be elucidated.

of the Study: This study aimed to investigate the expression characteristics of the IGF-1/IGFBP3 axis in UAP patients with SD-PTS and explore the mechanism by which JPQT stabilizes vulnerable atherosclerotic plaques in mice by regulating this axis and endothelial-mesenchymal transition (EndMT).

A quantitative proteomic analysis was conducted on plasma samples from UAP patients with SD-PTS, UAP patients with spleen deficiency phlegm-turbidity blood stasis syndrome (SD-PTBS), and healthy controls. Simultaneously, a high-fat diet was used to establish a mouse model of atherosclerotic vulnerable plaques with SD-PTS. The mice were randomly divided into six groups: normal control, model, atorvastatin, low-dose JPQT, medium-dose JPQT, and high-dose JPQT. After the intervention, plaque characteristics, serum levels of IGF-1/IGFBP3, and the expression of EndMT-related markers in aortic tissue were analyzed using histopathological staining, Western blotting, ELISA, and RT-qPCR.

Proteomic analysis revealed that plasma IGFBP3 levels were significantly upregulated in UAP patients with SD-PTS compared to UAP patients with SD-PTBS, and it was identified as a core target associated with this syndrome. In the mouse model, compared to the normal control group, the model group exhibited significantly reduced IGF-1 levels, elevated IGFBP3 levels, abnormal activation of EndMT, and increased plaque vulnerability. Intervention with the JPQT significantly reversed these alterations, the plaque stability improved.

The imbalance of the IGF-1/IGFBP3 axis and abnormal activation of EndMT are important pathological mechanisms in UAP with SD-PTS. JPQT can effectively stabilize atherosclerotic vulnerable plaques by regulating the balance of the IGF-1/IGFBP3 axis and inhibiting EndMT, providing a scientific basis for its clinical application.