Interleukin-10 promotes proliferation of vascular smooth muscle cells by inhibiting inflammation in rabbit abdominal aortic aneurysm

The formation and rupture of aneurysms is a reversible process involving the destruction and repair of smooth muscle cells, and the proliferation of vascular smooth muscle cells (VSMC) and inflammation play an important role. In our study, we investigated whether Interleukin-10 (IL-10) treatment delays and prevents the development of aneurysms, and the molecular mechanism whereby IL-10 could inhibit proliferation of VSMC by inhibiting inflammatory responses in abdominal aortic aneurysms.

With treatment by IL-10, the development of rabbit abdominal aortic aneurysm was delayed. The molecular mechanism may have been that IL-10 treatment inhibits inflammation in aneurysm tissue by promoting the activation of M2 macrophages and altering Th1/Th2 cytokine production.Tthe inhibited inflammatory response promoted the proliferation and phenotypic transformation of VSMC.

Models of rabbit abdominal aortic aneurysm (AAA) were established by elastin pressurization and perfusion, and recombinant IL-10 was used as a drug to intervene in treatment of the AAA model by rabbit ear vein injection. 1 week, 2 weeks and 4 weeks after establishing the AAA model, color Doppler ultrasound and H&E staining was used to observe the development of AAA. Western blotting and RT-qPCR were used to detect the gene expression of PCNA, OPN and α-SMA, Th1/Th2 cytokines were detected by RT-qPCR, Nf-kB and MCP-1 protein was analyzed by immunochemistry. Activation of Macrophage was analyzed by immunofluorescence.

Compared with the model group without any intervention, after treatment with IL-10, a decreased cell number was recorded and number of layers of smooth muscle cells in rabbit abdominal aortic aneurysms were significantly reduced, as was elastin breakage and smooth muscle cell degradation. The gene expression of PCNA and OPN, the mRNA expression of IFN-γ and TNF-α, and the protein expression of NF-kB and MCP-1 were elevated (P < 0.05), but α-SMA, IFN-γ, TNF-α, IL-4 and IL-13 were decreased (P < 0.05) in abdominal aortic aneurysm. The M2/M1 macrophage ratio increased significantly.