Hyperlipidemia is necessary for the initiation and progression of atherosclerosis by severe periodontitis in mice

Mol Med Rep. 2022 Aug;26(2):273. doi: 10.3892/mmr.2022.12789. Epub 2022 Jul 7.

Abstract

Hyperlipidemia is a major risk of atherosclerosis; however, systemic inflammatory diseases such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus and systemic sclerosis are also known risks for the development of atherosclerosis. Periodontitis, a local and systemic inflammatory condition, has also been reported as a risk for atherosclerosis, but the specific link between periodontitis and atherosclerosis remains somewhat controversial. We previously reported that ligature‑induced periodontitis exacerbates atherosclerosis in hyperlipidemic Apolipoprotein E‑deficient (ApoE‑/‑) mice. To understand whether hyperlipidemia is necessary for the development and exacerbation of atherosclerosis associated with periodontitis, the present study created ligature‑induced periodontitis in both wild‑type (WT) and ApoE‑/‑ mice. Subsequently, the status of local, systemic and vascular inflammation, serum lipid contents and arterial lipid deposition were examined with histological analysis, µCT, en face analysis, serum lipid and cytokine measurements, reverse transcription‑quantitative PCR and immunohistochemical analysis. Ligature placement induced severe periodontitis in both WT and ApoE‑/‑ mice at the local level as demonstrated by gingival inflammation, alveolar bone loss, increased osteoclastic activities and inflammation in alveolar bone. Systemic inflammation was also induced by ligature placement in both WT and ApoE‑/‑ mice, albeit more so in ApoE‑/‑ mice. The serum cholesterol levels were not altered by the ligature in both WT and ApoE‑/‑ mice. However, the vascular inflammation and arterial lipid deposition were induced by ligature‑induced periodontitis only in ApoE‑/‑ mice, but not in WT mice. The present study indicated that the coupling of systemic inflammation and hyperlipidemia was necessary for the development and exacerbation of atherosclerosis induced by ligature‑induced periodontitis in mice.

Keywords: atherosclerosis; hyperlipidemias; periodontitis; systemic inflammation.

MeSH terms

  • Animals
  • Apolipoproteins E
  • Atherosclerosis* / etiology
  • Atherosclerosis* / pathology
  • Disease Models, Animal
  • Hyperlipidemias* / complications
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Periodontitis* / complications

Substances

  • Apolipoproteins E