Zhao Shuai, Hua Xiumeng, Zhu Dongxing, Li Peiyuan, Cui Hao, Sun Zhe, Wang Yifan, Zhao Yiqi, Yang Xingyue, Wang Weiteng, Li Yijing, Zhang Hang, Mo Han, Dong Fei, Gu Yuanping, Chen Xiao, Fu Xiaodong, Song Jiangping
School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511495, Guangdong, China.
Beijing Key Laboratory of Xenotransplantation, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
BMC Med. 2026 Mar 16. doi: 10.1186/s12916-026-04798-9.
Hypertension-associated aortic dissection (HTN-AD) features intense immune activation and extracellular matrix disruption, yet the cellular programs that promote aortic-wall stabilization remain unclear. We aimed to identify macrophage states associated with vascular integrity and to determine whether these states could be mechanistically or therapeutically leveraged.
Single-cell RNA sequencing was performed on thoracic aortas from HTN-AD, Marfan syndrome-associated AD, and donor controls (n = 3 per group). Peripheral and tear-adjacent blood samples were analyzed in patients with HTN-AD, MS-AD, and healthy donors (n = 30 per group), with paired intraoperative tear-adjacent sampling performed when available (n = 10). Circulating monocytes and serum cytokines were profiled by flow cytometry and ELISA. Functional validation included TGF-β1 conditioning of human monocytes and murine macrophages and adoptive transfer experiments in a murine AD model.
A distinct SPP1 fibrogenic macrophage population was enriched in diseased aortas and transcriptionally bridged low-inflammatory macrophages and matrix-active states. Patients with HTN-AD displayed increased tear-adjacent non-classical monocytes and higher monocytic SPP1, correlating with serum TGF-β1 and a shorter ICU stay. TGF-β1 induced an SPP1-dependent fibrogenic program in macrophages while suppressing inflammatory markers. Myeloid Spp1 deficiency aggravated aortic dilatation and wall disruption, whereas adoptive transfer of TGF-β1-conditioned SPP1 macrophages reduced false lumen formation, improved collagen organization, decreased IL-1β and IL-6 expression, and enhanced survival.
A TGF-β1-SPP1 axis drives the emergence of SPP1 fibrogenic macrophages that support structural stabilization of the dissected aorta. Targeting this reparative myeloid program may offer a mechanistically informed therapeutic strategy for acute aortic syndromes.
高血压相关主动脉夹层（HTN-AD）的特征是强烈的免疫激活和细胞外基质破坏，但促进主动脉壁稳定的细胞程序仍不清楚。我们旨在确定与血管完整性相关的巨噬细胞状态，并确定这些状态是否可以通过机制或治疗手段加以利用。
对HTN-AD、马凡综合征相关AD和供体对照的胸主动脉进行单细胞RNA测序（每组n = 3）。对HTN-AD、MS-AD患者和健康供体的外周血和撕裂旁血样本进行分析（每组n = 30），如有条件则进行配对术中撕裂旁采样（n = 10）。通过流式细胞术和ELISA对循环单核细胞和血清细胞因子进行分析。功能验证包括对人单核细胞和小鼠巨噬细胞进行TGF-β1处理，以及在小鼠AD模型中进行过继转移实验。
在病变主动脉中富集了一个独特的SPP1促纤维化巨噬细胞群体，其在转录上连接了低炎症巨噬细胞和基质活性状态。HTN-AD患者撕裂旁非经典单核细胞增加，单核细胞SPP1水平升高，与血清TGF-β1和较短的ICU住院时间相关。TGF-β1在巨噬细胞中诱导了一个依赖SPP1的促纤维化程序，同时抑制炎症标志物。髓系Spp1缺陷加重了主动脉扩张和壁破坏，而TGF-β1处理的SPP1巨噬细胞的过继转移减少了假腔形成，改善了胶原组织，降低了IL-1β和IL-6表达，并提高了生存率。
TGF-β1-SPP1轴驱动了支持夹层主动脉结构稳定的SPP1促纤维化巨噬细胞的出现。靶向这一修复性髓系程序可能为急性主动脉综合征提供一种基于机制的治疗策略。
