Pan Liting, Chen Junji, Sun Yanjun, Wang Fang
Department of Cardiology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, 201803 Shanghai, China.
Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China.
Rev Cardiovasc Med. 2025 Jul 18;26(7):33511. doi: 10.31083/RCM33511. eCollection 2025 Jul.
Abdominal aortic aneurysm (AAA) is a major public health challenge and presents high mortality due to diagnostic and therapeutic difficulties. This study investigated the role of high-mobility group box2 (HMGB2) and the HMGB2-triggering receptor expressed on the myeloid cell (TREM) pathway in male AAA patients. The goal was to evaluate HMGB2 as a novel biomarker and to elucidate its contribution to the pathogenesis of AAA. Our findings offer new insights into AAA biology and highlight the potential application of HMGB2 for early detection and therapeutic targeting.
This retrospective case-control study included 36 male AAA patients and 41 male controls with balanced baseline characteristics. HMGB1, HMGB2, soluble TREM-1 (sTREM-1), and sTREM-2 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). The association between HMGB2 and AAA was analyzed using multivariate logistic regression, while the diagnostic performance of HMGB2 was assessed using receiver operating characteristic (ROC) curves.
Elevated HMGB2 and HMGB1 levels were associated with higher risks of AAA (HMGB2: OR: 1.158, 95% CI: 1.011-1.325; < 0.05; HMGB1: OR: 1.275, 95% CI: 1.048-1.551; < 0.05) and aneurysm rupture (HMGB2: OR: 1.117, 95% CI: 1.005-1.241; < 0.05; HMGB1: OR: 1.212, 95% CI: 1.003-1.465; < 0.05). Meanwhile, sTREM-1 exhibited a negative correlation with AAA (OR: 0.991, 95% CI: 0.985-0.997; < 0.01). The odds ratios of the fourth quartile HMGB2 and HMGB1 levels for AAA were 6.925-fold and 8.621-fold higher, respectively, than the first quartile levels. The HMGB2 serum level was positively correlated with a larger AAA diameter, with the diameter increasing progressively as the HMGB2 level increased. The area under the ROC curve (AUC) for predicting AAA was 0.713 for HMGB2, 0.677 for HMGB1, and 0.665 for sTREM-1. HMGB1 and sTREM-1 both correlated with HMGB2. Each HMGB1 quartile group exhibited a significant increase as HMGB2 increased. Further, sTREM-1 significantly increased at low to moderate HMGB2 levels but decreased in the highest HMGB2 quartile.
Elevated HMGB2 serum levels are independently associated with the incidence of AAA in males. HMGB2-TREM pathway disruption may play a critical role in AAA pathogenesis.
腹主动脉瘤（AAA）是一项重大的公共卫生挑战，因其诊断和治疗困难而具有较高的死亡率。本研究调查了高迁移率族蛋白B2（HMGB2）和髓样细胞上表达的触发受体（TREM）途径在男性AAA患者中的作用。目的是评估HMGB2作为一种新型生物标志物，并阐明其对AAA发病机制的贡献。我们的研究结果为AAA生物学提供了新的见解，并突出了HMGB2在早期检测和治疗靶点方面的潜在应用。
这项回顾性病例对照研究纳入了36例男性AAA患者和41例具有均衡基线特征的男性对照。通过酶联免疫吸附测定（ELISA）测量HMGB1、HMGB2、可溶性TREM-1（sTREM-1）和sTREM-2血清水平。使用多因素逻辑回归分析HMGB2与AAA之间的关联，同时使用受试者工作特征（ROC）曲线评估HMGB2的诊断性能。
HMGB2和HMGB1水平升高与AAA风险增加相关（HMGB2：比值比[OR]：1.158，95%置信区间[CI]：1.011 - 1.325；P < 0.05；HMGB1：OR：1.275，95% CI：1.048 - 1.551；P < 0.05）以及动脉瘤破裂风险增加相关（HMGB2：OR：1.117，95% CI：1.005 - 1.241；P < 0.05；HMGB1：OR：1.212，95% CI：1.003 - 1.465；P < 0.05）。同时，sTREM-1与AAA呈负相关（OR：0.991，95% CI：0.985 - 0.997；P < 0.01）。AAA患者中HMGB2和HMGB1水平第四四分位数的比值比分别比第一四分位数水平高6.925倍和8.621倍。HMGB2血清水平与更大的AAA直径呈正相关，随着HMGB2水平升高，直径逐渐增大。预测AAA的ROC曲线下面积（AUC），HMGB2为0.713，HMGB1为0.677，sTREM-1为0.665。HMGB1和sTREM-1均与HMGB2相关。随着HMGB2升高，每个HMGB1四分位数组均显著增加。此外，sTREM-1在低至中等HMGB2水平时显著增加，但在最高HMGB2四分位数时降低。
男性中升高的HMGB2血清水平与AAA的发病率独立相关。HMGB2 - TREM途径破坏可能在AAA发病机制中起关键作用。
