Mustafa Baris Kemahli, Cuneyt Narin, Cagatay Bilen, Pinar Akokay, Tugra Gencpinar, Kivanc Metin, Serdar Bayrak
Turkish Journal of Vascular Surgery - 2026;35(1):7-13
Aim: Abdominal aortic aneurysm is a progressive enlargement of the abdominal aorta associated with high mortality risk. Despite advances in surgical and endovascular treatments, no pharmacological therapy has been established to prevent aneurysm growth. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has demonstrated cardiovascular benefits beyond glycemic control. The aim of this study was to investigate the effects of dapagliflozin in a calcium phosphate-induced rat model of abdominal aortic aneurysm. Material and Methods: Twenty male Wistar albino rats were randomly divided into three groups: sham operated rats (Sham, n=6), rats with abdominal aortic aneurysm induced by calcium phosphate (AAA, n=7), and rats with aneurysm treated with dapagliflozin (Dapagliflozin group, n=7). Aneurysm formation was induced by periaortic application of calcium phosphate. The Dapagliflozin group received daily oral dapagliflozin at a dose of 1 mg/kg for 28 days. Morphometric parameters including lumen area, lumen plus intima area, and lumen plus intima plus media area were evaluated using hematoxylin-eosin staining. Elastin degradation was assessed with Van Gieson staining, vascular calcification with Alizarin Red staining, and apoptosis with immunohistochemical detection of Caspase-3 and Caspase-9. Statistical analyses were performed using Student's t-test and Mann-Whitney U test, with a significance threshold of p<0.05. Results: Morphometric parameters were significantly increased in the AAA group compared with the Sham group (all p<0.001). These parameters were reduced in the Dapagliflozin group compared with the AAA group (all p<0.001). Elastin degradation and calcium deposition were higher in the AAA group compared with Sham (p=0.001 and p=0.002) and decreased with dapagliflozin treatment (p=0.001 and p=0.012). Caspase-3 and Caspase-9 expression was elevated in the AAA group (p=0.002 and p=0.003) and decreased in the Dapagliflozin group, although the reduction in Caspase-9 did not reach statistical significance (p=0.068). Conclusion: Dapagliflozin reduced aortic dilatation, elastin degradation, vascular calcification, and Caspase-3-mediated apoptosis in a calcium phosphate-induced rat model of abdominal aortic aneurysm. These findings suggest that dapagliflozin exerts protective effects on vascular integrity beyond glucose regulation and may represent a potential medical therapy for abdominal aortic aneurysm.
