Metformin Does Not Attenuate Angiotensin II-Induced Aortic Aneurysms in Low-Density Lipoprotein Receptor Deficient Mice
Abstract
BACKGROUND: Metformin, a biguanide antihyperglycemic agent, prevents angiotensin II (AngII)-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient (ApoE-/-) mice. Low-density lipoprotein receptor-deficient (LDLR-/-) mice are also widely used as a hypercholesterolemic model, which more closely mimics the lipoprotein profile of patients with hypercholesterolemia than ApoE-/- mice. In addition, LDLR-/- mice exhibit characteristics of glucose metabolism that are distinct from ApoE-/- mice. However, it remains unknown whether metformin suppresses AngII-induced aortic aneurysm formation in LDLR-/- mice.
METHODS: Male LDLR-/- mice at 9 weeks of age were administered either vehicle or metformin in drinking water and fed a Western diet. Subsequently, AngII was infused into mice for 4 weeks. Plasma metformin concentrations were measured by mass spectrometry. Maximal aortic diameters and areas were measured ex vivo.
RESULTS: Mass spectrometry analysis determined plasma metformin concentrations in mice administered the drug. Metformin administration resulted in lower body weight compared to the vehicle group, indicating effective metformin administration. However, ex vivo measurements demonstrated that metformin did not reduce aortic diameters in the suprarenal abdominal region. In addition, metformin failed to prevent AngII-induced ascending aortic dilatations.
CONCLUSION: Metformin did not attenuate AngII-induced aortic aneurysm formation in either the ascending or…
How strong is the evidence?
Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.