Research on the mechanism of smooth muscle cell gp130 in abdominal aortic aneurysm
Objective To explore the impact of the interleukin-6 cytokine family co-receptor glycoprotein 130(gp130)on vascular smooth muscle cell phenotype and abdominal aortic aneurysm(AAA),identifying potential new targets for AAA prevention and treatment.Methods Smooth muscle cell gp130 knockout was induced by administering tamoxifen[0.1 mg/(g·d)]via intraperitoneal injection to Sm22-ER-Cre+gp130loxP/loxP mice for five consecutive days.A total of 17 eight-week-old smooth muscle-specific gp130 knockout(CKO)and control mice were selected.Both groups underwent combined Pcsk9 adeno-associated virus via tail vein injection(1×1011 v.g.),high-fat feeding,and angiotensin Ⅱ infusion[1 000 ng/(min·kg)for 28 days]to establish a mouse model of AAA.Vascular ultrasound was used to monitor changes in abdominal aortic diameter,with aneurysm formation defined as an increase of more than 50％in maximum outer diameter compared to baseline.EVG staining assessed the rupture of vascular elastic laminae.Real-time quantitative PCR,Western blotting,and immunohistochemistry analyzed the expression of contraction-related and inflammation-related genes.Collagen contraction assays evaluated the contraction function of primary mouse vascular smooth muscle cells.Results Compared to the control group,CKO mice showed a reduced incidence of AAA(P<0.05),decreased vascular diameter(P<0.05),and improved elastic lamina integrity.Expression of contraction-related genes(a-Sma,Sm22,etc.)was upregulated in CKO mice,while inflammation-related genes(Ccl2,Il-6,etc.)were downregulated,accompanied by reduced inflammatory cell infiltration.Isolated primary CKO vascular smooth muscle cells exhibited enhanced contraction function compared to control cells(P<0.05).Conclusions Smooth muscle cell-specific knockout of gp130 protects against the progression of AAA by maintaining smooth muscle cell contraction phenotype and function,as well as alleviating vascular inflammation.
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