Department of Cardiovascular Ultrasound, the First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
Department of Vascular and Thyroid Surgery, the First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
BMC Cardiovasc Disord. 2021 Aug 4;21(1):378. doi: 10.1186/s12872-021-02193-1.
Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) have been investigated to play significant roles in the formation of abdominal aortic aneurysm (AAA). But the reports on the expression pattern of TLR4 and MMP9 in human AAA specimens were relatively scant. The aim of this study was to make a detailed analysis of TLR4 and MMP9 expression in situ and their association with clinical parameters involved in human AAA.
40 AAA specimens were obtained from full-thickness aneurysmal tissues at the maximal dilation area during the open surgical repair, and 8 non-aneurysmal abdominal aortas from transplant donors served as controls. Expression of TLR4 and MMP9 protein was determined by immunohistochemistry.
There were increased levels of TLR4 and MMP9 expression in human AAA tissues. Compared with macrophages or SMCs, lymphocytes showed a higher positive rate of TLR4 and MMP9 staining, and an elevated ratio of high MMP9 expression (all P < 0.05). There existed a significant association between TLR4 and MMP9 expression (r = 0.767, P < 0.001), and both TLR4 and MMP9 levels were statistically related to circulating CRP. Moreover, TLR4 expression in situ indicated a positive correlation with its serum level (r = 0.654, P = 0.006). Multiple analysis revealed that high TLR4 expression in situ was associated with the risk of large AAA (OR = 6.211, 95%CI = 1.226-31.480, P = 0.027), while high MMP9 expression was correlated to the presence of thrombus within AAA (OR = 5.494, 95%CI = 1.181-25.562, P = 0.030), separately compared with their low expression.
This study confirmed the overexpression of TLR4 and MMP9 in human AAA tissues, and their close relationship implying in the pathogenesis of AAA. We further provided evidence that TLR4 had a potential effect on AAA size and MMP9 could influence the occurrence of thrombus within AAA.
Toll 样受体 4（TLR4）和基质金属蛋白酶 9（MMP9）已被研究在腹主动脉瘤（AAA）的形成中发挥重要作用。但是，关于 TLR4 和 MMP9 在人类 AAA 标本中的表达模式的报道相对较少。本研究旨在详细分析 TLR4 和 MMP9 在原位的表达及其与涉及人类 AAA 的临床参数的关联。
从开放手术修复过程中最大扩张区域的全层动脉瘤组织中获得 40 个 AAA 标本，从移植供体的 8 个非动脉瘤腹主动脉中获得 8 个作为对照。通过免疫组织化学测定 TLR4 和 MMP9 蛋白的表达。
人类 AAA 组织中 TLR4 和 MMP9 的表达水平增加。与巨噬细胞或 SMC 相比，淋巴细胞显示出更高的 TLR4 和 MMP9 染色阳性率，并且高 MMP9 表达的比例升高（均 P < 0.05）。TLR4 和 MMP9 表达之间存在显著相关性（r = 0.767，P < 0.001），并且 TLR4 和 MMP9 水平均与循环 CRP 统计学相关。此外，原位 TLR4 表达与血清水平呈正相关（r = 0.654，P = 0.006）。多元分析显示，原位高 TLR4 表达与大型 AAA 的风险相关（OR = 6.211，95%CI = 1.226-31.480，P = 0.027），而 MMP9 高表达与 AAA 内血栓的存在相关（OR = 5.494，95%CI = 1.181-25.562，P = 0.030），与低表达相比。
本研究证实了 TLR4 和 MMP9 在人类 AAA 组织中的过度表达，以及它们在 AAA 发病机制中的密切关系。我们进一步提供了证据表明 TLR4 对 AAA 大小有潜在影响，而 MMP9 可能影响 AAA 内血栓的形成。
