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- W2996544379 abstract "Despite significant efforts to identify medical therapy for aneurysm growth, no effective substance has been approved for treating patients. Recent retrospective Veterans Affairs database studies have shown decreased abdominal aortic aneurysm (AAA) formation and growth in diabetic patients who are treated with metformin. In addition, there is some preclinical evidence showing that hyperglycemia and metformin decrease elastase-induced AAA formation in mice. In this study, we evaluated the effects of metformin on angiotensin II-induced AAA formation in mice. Male low-density lipoprotein receptor-deficient mice at the age of 9 weeks were administered metformin (300 mg/kg/d) in drinking water or drinking water alone through the study period (N = 12/group). Three days later, a saturated fat-enriched diet was begun to induce hypercholesterolemia. One week after the initiation of this special diet, all mice had mini-osmotic pumps (Alzet Model 2004; Durect Corp, Cupertino, Calif) subcutaneously implanted to deliver angiotensin II (1000 ng/kg/min) for 4 weeks. After termination, aortas were dissected, fixed, cleaned, and imaged ex vivo. Maximal aortic diameters were measured according to our standard technique (Fig 1). Two mice in the control group and one mouse in the metformin group died of aortic rupture in the abdominal region. No differences of maximal diameters were detected between the groups (control vs metformin: 1.6 ± 0.1 mm vs 1.4 ± 0.1 mm; P = .3 by Student t-test; Fig 2). The incidence of AAA was based on AAA rupture or 50% increase of normal aortic diameter (based on previous studies showing ∼0.9 mm is the mean of normal aortic diameter). No difference of AAA incidence was noted (control vs metformin: 8/12 vs 6/12; P = .7 by Fisher exact test). Despite the human clinical observation, metformin did not attenuate angiotensin II-induced AAA in mice. Hyperglycemia may have been the driving force in the human clinical database findings. Further investigation will be needed to determine whether hyperglycemia in combination with metformin reduces angiotensin II-induced AAA and into the mechanism of hyperglycemia attenuation of AAA.Fig 2Abdominal aortic width in angiotensin II-infused mice comparing the control drinking water cohort and metformin drinking water cohort.View Large Image Figure ViewerDownload Hi-res image Download (PPT)" @default.
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- W2996544379 date "2020-01-01" @default.
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- W2996544379 title "Metformin Does Not Attenuate Angiotensin II-Induced Abdominal Aortic Aneurysms in Low-Density Lipoprotein Receptor-Deficient Mice" @default.
- W2996544379 doi "https://doi.org/10.1016/j.jvs.2019.10.047" @default.
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