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

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 athero sclerosis. 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 ligatureinduced periodontitis exacerbates atherosclerosis in hyperlipidemic Apolipoprotein Edeficient (ApoE) mice. To understand whether hyperlipidemia is necessary for the devel opment and exacerbation of atherosclerosis associated with periodontitis, the present study created ligatureinduced peri odontitis in both wildtype (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 transcriptionquantitative 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 ligatureinduced 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 ligatureinduced periodontitis in mice.