Gene knockdown of angiopoietin-like protein 3 reduces the occurrence and development of thoracic aortic aneurysms

Objective To explore the role of angiopoietin-like protein 3 (ANGPTL3) in the development of thoracic aortic aneurysm (TAA) and its possible mechanism. Methods The TAA patients who underwent open surgical repair in Beijing Anzhen Hospital were selected as the experimental group (n=6), and the aortic tissue in the control group was obtained from a heart transplant donor (n=6). Another 30 3-week-old male C57BL/6J mice were randomly divided into control (control) and β-aminopropionitrile (BAPN)-induced TAA model groups (n=15 per group). The aortic tissue was taken 4 weeks later. Immunohistochemical method was used to detect the expression of ANGPTL3 in human thoracic aortic aneurysm tissue, immunohistochemistry were used to detect the expression of ANGPTL3, IL-6, MMP2, and MMP9 in mouse aortic tissue, and TUNEL method was used to detect apoptosis. Immunofluorescence co-localization was used to detect the localization of ANGPTL3 in vascular tissues. Transfect human aortic smooth muscle cells with ANGPTL3 siRNA. Observe the effect of ANGPTL3 knockdown on AngⅡ-induced smooth muscle cell apoptosis and inflammatory response. Results In the aortic tissues of patients with thoracic aortic aneurysm and TAA mice, the expression of ANGPTL3 protein increased significantly (P＜0.05), vascular smooth muscle cell apoptosis, and the protein expressions of inflammatory factors IL-1β, MMP2, and MMP9 were all significantly increased(P＜0.05). In addition, ANGPTL3 knockdown can significantly reduce AngⅡ-induced smooth muscle cell apoptosis and inflammatory factor secretion (P＜0.05). Conclusions The ANGPTL3 protein level is increased in the development of thoracic aortic aneurysm. Inhibition of ANGPTL3 protein expression can reduce the cell apoptosis and inflammation of smooth muscle cells. It suggests that targeting ANGPTL3 may inhibit the development of thoracic aortic aneurysms by inhibiting cell apoptosis and inflammation in smooth muscle.