Effects of a high-phosphate diet on vascular calcification and abdominal aortic aneurysm in mice

Vascular aging is an important risk factor for cardiovascular diseases, including abdominal aortic aneurysm (AAA) and pathological aortic dilatation, playing a critical role in the morbidity and mortality of older adults. Vascular calcification, a phenotype of vascular aging, is frequently associated with AAA. However, this association remains unclear owing to the lack of animal models. This study investigated the effects of a high-phosphate diet (HPD), a prominent trigger of vascular calcification in AAA.

Eight-week-old male mice were fed either a normal diet (ND; Ca 1.18%/P 1.07% = 1.10) or an HPD (Ca 1.23%/P 1.65% = 0.75) for 4 weeks. Subsequently, AAA was induced using CaCl₂ application and angiotensin II (AngII) infusion for 4 weeks.

The HPD resulted in more pronounced AAA formation than did the ND. Importantly, vascular calcification was observed only in the aorta of the HPD mice. Enhanced Runt-related transcription factor 2 expression and apoptosis (downregulation of growth arrest-specific gene 6/pAkt survival pathway), two major mechanisms of vascular calcification, were also observed. Furthermore, increased IL-6 and F4/80 expression was observed in the aorta of HPD mice. In RAW264.7 cells, inorganic phosphate enhanced IL-6 and IL-1β expression under AngII priming. Ferric citrate, a phosphate binder, significantly inhibited HPD-induced AAA formation.

These findings suggest that HPD induces vascular calcification and AAA formation, possibly through inflammation. This murine model suggests that vascular calcification induced by phosphate burden may be a therapeutic target for vascular diseases, including AAA. Geriatr Gerontol Int 2024; 24: 973-981.