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

Geriatr Gerontol Int. 2024 Sep;24(9):973-981. doi: 10.1111/ggi.14959. Epub 2024 Aug 14.

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: abdominal aortic aneurysm; apoptosis; inflammation; inorganic phosphate; vascular calcification.

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal* / chemically induced
  • Aortic Aneurysm, Abdominal* / etiology
  • Aortic Aneurysm, Abdominal* / metabolism
  • Aortic Aneurysm, Abdominal* / pathology
  • Apoptosis / drug effects
  • Disease Models, Animal*
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Phosphates* / adverse effects
  • Phosphates* / metabolism
  • Vascular Calcification* / etiology
  • Vascular Calcification* / metabolism

Substances

  • Phosphates