Zalghout Sara, Vo Sophie, Arocas Véronique, Jadoui Soumaya, Hamade Eva, Badran Bassam, Oudar Olivier, Charnaux Nathalie, Longrois Dan, Boulaftali Yacine, Bouton Marie-Christine, Richard Benjamin
LVTS, INSERM, U1148, Paris, France.
Université Sorbonne Paris Nord, Villetaneuse, France.
Front Cardiovasc Med. 2022 Apr 25;9:839743. doi: 10.3389/fcvm.2022.839743. eCollection 2022.
Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA ( = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA.
长期以来，糖胺聚糖（GAGs）积聚一直被视为与平滑肌细胞（SMCs）凋亡和弹性纤维降解一起定义胸主动脉瘤（TAA）的组织病理学特征之一。然而，关于GAGs的组成或它们在TAA病理学中的潜在影响，人们所知甚少。Syndecan-1（SDC-1）是一种硫酸乙酰肝素蛋白聚糖，参与细胞外基质（ECM）相互作用和组装、SMC表型调节以及血管壁炎症的各个方面。因此，本研究的目的是确定SDC-1表达在人类TAA中是否受到调控，并分析其在该疾病小鼠模型中的作用。在当前工作中，通过RT-qPCR、ELISA和免疫组织化学检测了人类活检组织中SDC-1的调控情况。此外，使用结合主动脉壁弱化和高血压的小鼠模型评估了SDC-1在降主动脉TAA中的作用。我们的结果表明，SDC-1 mRNA和蛋白在人类TAA标本的中膜层均过度表达。RT-qPCR实验显示SDC-1 mRNA过度表达3.6倍（P = 0.0024），ELISA分析表明，与健康对照相比，TAA样本中SDC-1蛋白增加了2.3倍（分别为221±24 vs. 96±33 pg/mg组织，P = 0.0012）。免疫荧光成像提供了证据，表明SMC是TAA中膜层表达SDC-1的主要细胞类型。同样，在所用的小鼠模型中，与健康样本相比，TAA标本中SDC-1表达增加。尽管已有报道其对腹主动脉瘤具有保护作用，但我们观察到SDC-1对于TAA的发生率或破裂并非必需。此外，在我们的TAA模型中，SDC-1缺陷并未改变主动脉壁扩张程度、弹性蛋白降解、胶原蛋白沉积或白细胞募集情况。这些发现表明SDC-1可能是揭示TAA病理学的生物标志物。未来的研究可能会揭示导致TAA中SDC-1表达调控的潜在机制。
