The Shapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, Los Angeles, CA 90095, USA.
Mol Med Rep. 2022 Aug;26(2). doi: 10.3892/mmr.2022.12789. Epub 2022 Jul 7.
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 () 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 mice. Subsequently, the status of local, systemic and vascular inflammation, serum lipid contents and arterial lipid deposition were examined with histological analysis, CT, analysis, serum lipid and cytokine measurements, reverse transcription‑quantitative PCR and immunohistochemical analysis. Ligature placement induced severe periodontitis in both WT and 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 mice, albeit more so in ApoE mice. The serum cholesterol levels were not altered by the ligature in both WT and mice. However, the vascular inflammation and arterial lipid deposition were induced by ligature‑induced periodontitis only in 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.
高脂血症是动脉粥样硬化的主要危险因素；然而，类风湿关节炎、银屑病、系统性红斑狼疮和系统性硬化症等系统性炎症性疾病也是动脉粥样硬化发展的已知危险因素。牙周炎是一种局部和全身炎症性疾病，也被报道为动脉粥样硬化的危险因素，但牙周炎与动脉粥样硬化之间的具体联系仍存在一些争议。我们之前报道过结扎诱导的牙周炎会加重高脂血症载脂蛋白 E 缺陷 () 小鼠的动脉粥样硬化。为了了解高脂血症是否是牙周炎相关动脉粥样硬化发生和加重的必要条件，本研究在野生型 (WT) 和 小鼠中建立了结扎诱导的牙周炎。随后，通过组织学分析、CT 分析、分析、血清脂质和细胞因子测量、逆转录定量 PCR 和免疫组织化学分析，检查了局部、全身和血管炎症、血清脂质和动脉脂质沉积的状态。结扎在 WT 和 小鼠的局部水平均诱导了严重的牙周炎，表现为牙龈炎症、牙槽骨丧失、破骨细胞活性增加和牙槽骨炎症。WT 和 小鼠的结扎也诱导了全身炎症，尽管在 ApoE 小鼠中更为明显。WT 和 小鼠的血清胆固醇水平不受结扎的影响。然而，血管炎症和动脉脂质沉积仅在 小鼠中由结扎诱导的牙周炎引起，而在 WT 小鼠中则没有。本研究表明，系统性炎症和高脂血症的结合是结扎诱导的牙周炎在小鼠中诱导动脉粥样硬化发生和加重的必要条件。
