Research on the correlation between activating transcription factor 3 expression in the human coronary artery and atherosclerotic plaque stability

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR

“…The HMDP represents an exciting repository to further investigate metabolic and cardiovascular traits in mouse models within a controlled environment [61,62,68]. Data from HMDP confirmed the relevant role of ATF3 in cholesterol metabolism.…”

“…LPS stimulation of mouse AML12 liver cells resulted in the same effect on MAFF and LDLR expression [22]. In line with the LPS-induced ATF3 upregulation, ATF3 expression has been subject to metabolic, inflammatory and atherosclerosis research before [23][24][25][26][27][60][61][62][63][64][65][66][67]. Specifically, ATF3 was shown to protect against LPS induced inflam-mation in mice via inhibiting HMGB1 expression.…”

Exploring the Potential of Proteome Analysis as a Promising Tool for Evaluation of Sudden Cardiac Death (SCD) in Forensic Settings: A Literature Review

“…In particular, this protein is involved in several pathological contexts, such as extracellular matrix dysfunction and the development of atherosclerosis, although it is not clear whether it is a promoter or an inhibitor of atherosclerosis mechanisms. In one study, Peng et al evaluated 68 coronary artery samples, of which 36 were cases of sudden death associated with plaque rupture with intra-plaque hemorrhage, while the remaining were the control group, i.e., they had coronary atherosclerosis but died of other causes [ 38 ]. Protein expression was analyzed using Western blotting.…”

“…The authors also evaluated the role of inflammatory factors with Western blot, i.e., TNF-alpha, IL-1B, CD-45, VCAM, and MMP-9, demonstrating a greater expression in the group of sudden deaths associated with plaque rupture. The study demonstrates how all these proteins could be evaluated as useful markers for the diagnosis of coronary plaque rupture, although standard investigation protocols are not yet known [ 38 ].…”

Characterization of global research trends and prospects on sudden coronary death: A literature visualization analysis

“…Plasma biomarkers, including not only traditional biomarkers like B type natriuretic peptide (BNP) [ 60 ] or troponin [ 18 ] but also inflammatory biomarkers as C -reactive protein (CRP) or high-sensitive CRP (hsCRP) [ 61 ], have improved CAD risk prediction. Moreover, researchers have investigated emerging biomarkers and further categories, such as inflammation (lpoprotein-associated phospholipase A2 [ 62 ], pentraxin-3 [ 63 ]), myocardial stress (soluble form of ST2 (18)), plaque stability (matrix metalloproteinase [ 64 ], transcription factor 3 [ 65 ], complement component 7 [ 66 ], OX40L and ICAM-1 [ 67 ]), myocardial fibrosis [ 68 , 69 ], RNA (circRNA [ [70] , [71] , [72] ], miRNA [ 73 , 74 ], mRNA [ 75 ]), and DNA (SNP[ 9 , 76 , 77 ], insertion/deletion [ 78 ]). We find that the significance of serum predictive biomarkers for sudden coronary death has been established in these studies.…”