Department of Stomatology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
J Cell Mol Med. 2024 Nov;28(21):e70187. doi: 10.1111/jcmm.70187.
Periodontitis is a significant independent risk factor for atherosclerosis. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the effect of exosomes-miR-155-5p derived from periodontal endothelial cells on atherosclerosis in vitro and in vivo. Higher expression of miR-155-5p was detected in the plasma exosomes of patients with chronic periodontitis (CP) and carotid atherosclerosis (CAS) compared to patients with CP. Also, the expression level of miR-155-5p was associated with the severity of CP. miR-155-5p-enriched exosomes from HUVECs increased the angiogenesis and permeability of HAECs and promoted the expression of angiogenesis, permeability, and inflammation genes. Along with the overexpression or inhibition of miR-155-5p, the biological effect of HUVECs-derived exosomes on HAECs changed correspondingly. In ApoE-/- mouse models, miR-155-5p-enriched exosomes promoted the occurrence of carotid atherosclerosis by increasing permeable and angiogenic activity. Collectively, these findings highlight a molecular mechanism of periodontitis in CAS, uncovering exosomal miR-155-5p derived periodontitis affecting carotid endothelial cells in an 'exosomecrine' manner. Exosomal miR-155-5p may be used as a biomarker and target for clinical intervention to control this intractable disease in future, and the graphic abstract was shown in Figure S1.
牙周炎是动脉粥样硬化的一个重要独立危险因素。然而,其确切作用机制仍不完全清楚。在这项研究中,我们研究了来源于牙周内皮细胞的外泌体 miR-155-5p 在体外和体内对动脉粥样硬化的影响。与慢性牙周炎(CP)患者相比,患有 CP 和颈动脉粥样硬化(CAS)的患者血浆外泌体中 miR-155-5p 的表达水平更高。此外,miR-155-5p 的表达水平与 CP 的严重程度相关。从 HUVECs 中分离出富含 miR-155-5p 的外泌体增加了 HAECs 的血管生成和通透性,并促进了血管生成、通透性和炎症基因的表达。随着 miR-155-5p 的过表达或抑制,HUVECs 衍生的外泌体对 HAECs 的生物学效应也相应发生变化。在 ApoE-/- 小鼠模型中,富含 miR-155-5p 的外泌体通过增加通透性和血管生成活性促进颈动脉粥样硬化的发生。总之,这些发现强调了牙周炎在 CAS 中的分子机制,揭示了来源于牙周炎的外泌体 miR-155-5p 以“外泌体分泌”的方式影响颈动脉内皮细胞。外泌体 miR-155-5p 可能作为未来控制这种难治性疾病的临床干预的生物标志物和靶点,其示意图如图 S1 所示。