Du Fenghe, Zhu Zhan, Lai Zhichao, Li Kang, Chen Junye, Zhang Erli, Wang Jing, Zhao Hongmei, Liu Bao
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, China; Peking Union Medical College, MD Program, No 9, Dong Dan San Tiao, Dongcheng District, Beijing, 100730, China.
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, China.
Microbes Infect. 2023 Nov-Dec;25(8):105181. doi: 10.1016/j.micinf.2023.105181. Epub 2023 Jul 7.
Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.
牙周病是一种常见的口腔疾病，是动脉粥样硬化的独立危险因素。牙龈卟啉单胞菌（P.g）是牙周病的关键病原体，它参与了动脉粥样硬化的发病过程。然而，确切机制仍不清楚。越来越多的研究提出了血管周围脂肪组织（PVAT）在包括高脂血症和糖尿病在内的病理状况下的致动脉粥样硬化作用。然而，PVAT在P.g感染促进的动脉粥样硬化中的作用尚未得到探索。在我们的研究中，我们通过对临床样本进行实验，研究了PVAT中P.g定植与动脉粥样硬化进展之间的关联。我们还进一步研究了20周、24周和28周龄的有或无P.g感染的C57BL/6 J小鼠中P.g对PVAT的侵袭、PVAT炎症、主动脉内皮炎症、主动脉脂质沉积和全身炎症。以Th1/Treg失衡和脂肪因子水平失调为特征的PVAT炎症与P.g侵袭有关，且先于与其直接侵袭无关的内皮炎症发生。全身炎症的表型与PVAT炎症一致，但全身炎症在内皮炎症之后发生。因此，在慢性P.g感染中，早期动脉粥样硬化中的PVAT炎症可能是主动脉内皮炎症和脂质沉积的主要触发因素，这是通过辅助性T细胞1相关脂肪因子的旁分泌分泌失调实现的。
