Hosaka Itaru, Ikegami Ippei, Mikami Takuma, Sato Tatsuya, Ogawa Toshifumi, Mukawa Kei, Tanaka Marenao, Endo Keisuke, Akiyama Yukinori, Ohkawa Akihito, Nakazawa Junji, Shibata Tsuyoshi, Nakajima Tomohiro, Iba Yutaka, Shiiku Chikara, Sumino Satoshi, Koshima Ryuji, Takano Kenichi, Ichimiya Shingo, Kawaharada Nobuyoshi, Furuhashi Masato
Department of Cardiovascular Surgery Sapporo Medical University School of Medicine Sapporo Japan.
Department of Human Immunology Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine Sapporo Japan.
J Am Heart Assoc. 2025 Mar 18;14(6):e040279. doi: 10.1161/JAHA.124.040279. Epub 2025 Feb 19.
Chronic inflammation is involved in the development of abdominal aortic aneurysm (AAA). A tertiary lymphoid structure (TLS) within vascular lesions has recently been focused on for its role in modulation of inflammation in local tissues. We aimed to elucidate the relationships between TLS and pathophysiology of AAA.
Abdominal aortic samples obtained from 37 patients with AAA (men/women: 34/3, age: 72.8±9.9 years) and 15 autopsied patients who died from non-aortic events (men/women: 11/4, age: 65.5±9.8 years) were investigated.
TLSs in AAA lesions were confirmed by focal infiltration of CD3-positive cells surrounding germinal center-like structures containing CD20-positive cells between the tunica adventitia and tunica media layers. The formation of a TLS was significantly more prevalent in AAA patients than in autopsied patients. The number of TLSs in AAA lesions was positively correlated with sac diameter (r=0.357, =0.035) and the amount of intraluminal thrombosis (r=0.466, =0.005). T cells and B cells were predominant cellular populations among CD45 cells in AAA lesions. There was a significantly positive correlation between the proportions of interfollicular T follicular helper (CD3CD4CD45RACXCR5PD-1) cells and double negative B (CD3CD19IgDCD27) cells, and they were positively correlated with sac diameter, intraluminal thrombosis, and serum lipids. Deposited single-cell RNA-sequencing data for AAA showed that T follicular helper cells and double negative B cells were associated with lipid metabolism, T cell activation/proliferation and inflammation.
The formation of a TLS in AAA lesions is associated with sac diameter and intraluminal thrombosis in connection with interfollicular T follicular helper cells and double negative B cells, which may contribute to the pathophysiology of AAA and might be novel therapeutic targets for the development of AAA.
慢性炎症参与腹主动脉瘤（AAA）的发展。血管病变内的三级淋巴结构（TLS）最近因其在调节局部组织炎症中的作用而受到关注。我们旨在阐明TLS与AAA病理生理学之间的关系。
研究了从37例AAA患者（男性/女性：34/3，年龄：72.8±9.9岁）和15例因非主动脉事件死亡的尸检患者（男性/女性：11/4，年龄：65.5±9.8岁）获得的腹主动脉样本。
通过在主动脉外膜和中膜层之间围绕含有CD20阳性细胞的生发中心样结构的CD3阳性细胞的局灶性浸润，证实了AAA病变中的TLS。TLS的形成在AAA患者中比在尸检患者中明显更普遍。AAA病变中TLS的数量与瘤体直径（r = 0.357，P = 0.035）和腔内血栓形成量（r = 0.466，P = 0.005）呈正相关。T细胞和B细胞是AAA病变中CD45细胞中的主要细胞群体。滤泡间T滤泡辅助细胞（CD3CD4CD45RACXCR5PD-1）和双阴性B细胞（CD3CD19IgDCD27）的比例之间存在显著正相关，并且它们与瘤体直径、腔内血栓形成和血脂呈正相关。AAA的沉积单细胞RNA测序数据显示，T滤泡辅助细胞和双阴性B细胞与脂质代谢、T细胞活化/增殖和炎症相关。
AAA病变中TLS的形成与瘤体直径和腔内血栓形成有关，与滤泡间T滤泡辅助细胞和双阴性B细胞有关，这可能有助于AAA的病理生理学，并且可能是AAA发展的新治疗靶点。
