Department of Forensic Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou, China.
BMC Cardiovasc Disord. 2021 Jul 28;21(1):356. doi: 10.1186/s12872-021-02161-9.
Activating transcription factor 3 (ATF3) is an early response gene that is activated in response to atherosclerotic stimulation and may be an important factor in inhibiting the progression of atherosclerosis. In this study, we directly measured the expression of ATF3 and inflammatory factors in human coronary atherosclerotic plaques to examine the relationship between ATF3 expression, inflammation and structural stability in human coronary atherosclerotic plaques.
A total of 68 coronary artery specimens were collected from the autopsy group, including 36 cases of sudden death from coronary heart disease (SCD group) and 32 cases of acute death caused by mechanical injury with coronary atherosclerosis (CHD group). Twenty-two patients who had no coronary heart disease were collected as the control group (Con group). The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the intimal and lesion thicknesses, thickness of the fibrous cap, thickness of necrosis core, degree of lumen stenosis were assessed by image analysis software. Western blotting and immunohistochemistry were used to measure the expression and distribution of ATF3, inflammatory factors (CD45, IL-1β, TNF-α) and matrix metalloproteinase-9 (MMP-9) and vascular cell adhesion molecule 1 (VCAM1) in the coronary artery. The Pearson correlation coefficient was used to analyse the correlation between ATF3 protein expression and inflammatory factors and between ATF3 protein expression and structure-related indexes in the lesion group.
Compared with those in the control group, the intima and necrotic core in the coronary artery were thickened, the fibrous cap became thin and the degree of vascular stenosis was increased in the lesion group, while the intima and necrotic core became thicker and the fibrous cap became thinner in the SCD group than in the CHD group (P < 0.05). There was no or low expression of ATF3, inflammatory factors, VCAM1 and MMP-9 in the control group, and the expression of inflammatory factors, VCAM1 and MMP-9 in the SCD group was higher than that in CHD group, while the expression of ATF3 in the SCD group was significantly lower than that in CHD group (P < 0.05). In the lesion group, the expression of ATF3 was negatively correlated with intimal and necrotic focus thickness, positively correlated with fibrous cap thickness (P < 0.01), and negatively correlated with inflammatory factors, VCAM1 and MMP-9 (P < 0.01).
The expression of ATF3 may be related to the progression and stability of atherosclerotic plaques, and may affect the structural stability of atherosclerotic plaques by regulating the inflammatory response, thus participating in the regulation of atherosclerotic progression.
激活转录因子 3（ATF3）是一种早期反应基因，可被动脉粥样硬化刺激激活，可能是抑制动脉粥样硬化进展的重要因素。在本研究中，我们直接测量了人冠状动脉粥样硬化斑块中 ATF3 和炎症因子的表达，以研究 ATF3 表达、炎症与人类冠状动脉粥样硬化斑块结构稳定性之间的关系。
共收集 68 例冠状动脉标本，其中 36 例为冠心病猝死（SCD 组），32 例为机械性损伤合并冠状动脉粥样硬化（CHD 组）所致急性死亡，22 例无冠心病患者作为对照组（Con 组）。常规 HE 染色后，在光镜下观察冠状动脉的组织学结构，采用图像分析软件评估内膜和病变厚度、纤维帽厚度、坏死核心厚度、管腔狭窄程度。采用 Western blot 和免疫组化法测量冠状动脉中 ATF3、炎症因子（CD45、IL-1β、TNF-α）和基质金属蛋白酶-9（MMP-9）和血管细胞黏附分子 1（VCAM1）的表达和分布。采用 Pearson 相关系数分析病变组 ATF3 蛋白表达与炎症因子之间以及 ATF3 蛋白表达与结构相关指标之间的相关性。
与对照组相比，病变组的冠状动脉内膜和坏死核心增厚，纤维帽变薄，血管狭窄程度增加，而 SCD 组的内膜和坏死核心比 CHD 组更厚，纤维帽更薄（P<0.05）。对照组 ATF3、炎症因子、VCAM1 和 MMP-9 表达水平较低或无表达，SCD 组炎症因子、VCAM1 和 MMP-9 表达水平高于 CHD 组，而 SCD 组 ATF3 表达水平明显低于 CHD 组（P<0.05）。在病变组中，ATF3 的表达与内膜和坏死核心厚度呈负相关，与纤维帽厚度呈正相关（P<0.01），与炎症因子、VCAM1 和 MMP-9 呈负相关（P<0.01）。
ATF3 的表达可能与动脉粥样硬化斑块的进展和稳定性有关，可能通过调节炎症反应影响动脉粥样硬化斑块的结构稳定性，从而参与动脉粥样硬化的进展调节。
