Correlation analysis of serum endothelial cell specific molecule-1, endothelial microparticles, hypoxia inducible factor-1α levels and acute myocardial infarction and their predictive value for major adverse cardiovascular events: a retrospective study

Introduction

Acute myocardial infarction (AMI), the ischaemic necrosis of the myocardium, is an acute and critical type of coronary heart disease. Its clinical manifestations are persistent severe retrosternal pain, often accompanied by a sense of impending death and fever. Cardiac troponin I (cTnI) is the key biomarker of AMI (Kala et al., 2024). Major adverse cardiovascular events (MACEs) are a substantially hazard to the mental and physical well-being of patients with AMI and may occur after therapy. MACEs include recurrent myocardial infarction, cardiac failure, angioplasty and mortality. Therefore, their early diagnosis has important clinical significance. Hypoxia inducible factor-1α (HIF-1α) (Dölling et al., 2022), endothelial microparticle (EMP) (Yuan, Maitusong & Muyesai, 2020) and endothelial cell specific molecule-1 (ESM-1) (Wei et al., 2022) levels are associated with AMI. HIF-1α is sensitive to hypoxic environments; its level rapidly increases when the body’s myocardial cells are in a state of ischaemia and then decrease after correction. EMPs are mainly synthesised by endothelial cells in hypoxia or inflammatory environment and can further accelerate the atherosclerotic response of the body. ESM-1 is mainly secreted by activated endothelial cells and closely related to cardiovascular diseases, and its expression is regulated by various cytokines. This study aimed to examine the association of ESM-1, EMP and HIF-1α serum levels with AMI and their predictive value for MACEs in 106 patients with AMI admitted to our hospital between October 2020 and October 2022. The subsequent outcomes are given as follows.

Results

Analysis of the relationship between general information and MACE in patients with AMI

No substantial difference (P > 0.05) in demographic characteristics such as gender, age, body mass index, prevalence of vascular disease, hypertension, diabetes or smoking situation was found between the two groups (Table 3). Additionally, no significant differences in treatment details and blood routine parameters were observed between the two groups (P > 0.05) (Table 4 and Fig. 1).

Table 3:

Examines the correlation between general information and MACEs in individuals with AMI.

Clinical data	Good prognosis (n = 65)	Poor prognosis (n = 41)	Statistic	P
Sexuality (n (%))			0.520	0.471
Male	30 (46.15%)	16 (39.02%)
Female	35 (53.85%)	25 (60.98%)
Age (X ± S, years)	63.18 ± 8.21	63.12 ± 8.17	0.031	0.975
Body mass index (BMI) (X ± S, kg/m2)	25.87 ± 2.67	25.76 ± 2.54	0.209	0.835
Number of diseased vessels (n (%))			2.546	0.280
Single branch	26 (40%)	20 (48.78%)
Double branch	17 (26.15%)	13 (31.71%)
Three branches	22 (33.85%)	8 (19.51%)
Hypertension (n (%))	31 (47.69%)	24 (58.54%)	1.184	0.276
Diabetes (n (%))	28 (43.08%)	22 (53.66%)	1.130	0.288
Smoking (n (%))	30 (46.15%)	20 (48.78%)	0.070	0.792

DOI: 10.7717/peerj.19111/table-3

Table 4:

Treatment details in individuals with AMI (n (%)).

Clinical data	Good prognosis (n = 65)	Poor prognosis (n = 41)	Statistic	P
Percutaneous coronary intervention (n (%))	56 (86.15%)	36 (87.8%)	0.060	0.807
Beta-blocker (n (%))	55 (84.62%)	33 (80.49%)	0.304	0.581
Renin-angiotensin system (RAS) blocker (n (%))	55 (84.62%)	34 (82.93%)	0.053	0.818

DOI: 10.7717/peerj.19111/table-4

Predictive value of serum HIF-1α, EMP and ESM-1 expression for MACE

The ROC curve was generated using the serum amounts of HIF-1α, EMPs, and ESM-1 in individuals with AMI as the independent variable and MACE as the dependent variable (1 = Yes, 0 = No). A high diagnostic value was found for the combined evaluation of HIF-1α, EMP, and ESM-1 serum levels in predicting MACE (area under the curve (AUC) = 0.931) (Table 6 and Fig. 2).

Table 6:

Predictive value of serum HIF-1α, EMPs and ESM-1 expression for MACEs.

Index	AUC	95% CI	Optimal cut-off value	Specificity	Sensitivity
HIF-1α	0.784	0.820–0.927	44.615/(ng/L)	0.680	0.852
EMPs	0.896	0.954–0.979	390.000/(/μL)	0.720	0.938
ESM-1	0.746	0.005–0.275	1.245/(ng/mL)	0.720	0.802

DOI: 10.7717/peerj.19111/table-6

Discussion

AMI is a common clinical cardiovascular disease mainly caused by acute coronary artery occlusion for various reasons, resulting in partial coronary artery stenosis and myocardial tissue ischaemia, hypoxic necrosis or softening. If standard treatment is not given timely, this condition may lead to arrhythmia, heart failure and other serious heart diseases which can greatly affect the life of patients (Ducrocq et al., 2021; Damluji et al., 2021). Therefore, the early diagnosis of AMI and MACE can provide basis for clinical implementation of timely and effective prevention and treatment measures.

Logistic regression analysis revealed that high serum HIF-1α (OR = 1.819), EMP (OR = 1.071), and ESM-1 (OR = 14.655) levels were all found to be independent risk variables for AMI. A high diagnostic value was indicated by the ROC curve, which showed that the combined measurement of blood HIF-1α, EMP, and ESM-1 levels for predicting MACEs had an AUC of 0.931. MACEs are strongly linked to serum HIF-1α (OR = 18.716), EMPs (OR = 26.185) and ESM-1 (OR = 13.992).

Microparticles (MPs), also known as microvesicles, are lipid membrane vesicles (0.1–1 µm in diameter) released by cells (including platelets, white blood cells, endothelial cells, red blood cells and vascular smooth muscle cells) during activation or apoptosis (Luo et al., 2017). When released, MPs obtain the surface antigen and cytoplasmic components of the mother cells, which enable them to mark the changes of the mother cells and serve as a marker for various diseases. Moreover, MPs can facilitate information transmission between cells by carrying mRNA and microRNA, thus playing an important biological role and even participate in the occurrence of diseases (Ma et al., 2023). EMPs are mainly produced due to endothelial cell dysfunction. In addition to being a substitute for early endothelial cell dysfunction, EMPs are an important biological molecule regulating inflammation and coagulation after early endothelial cell injury (Mörtberg et al., 2019). AMI causes a series of inflammatory reactions in the body which can stimulate the mass accumulation of calcium ions and activate calpain, thereby causing the cleavage and recombination of endothelial cytoskeleton in the anaerobic environment; EMPs are the products of the recombination of endothelial cells (Liang et al., 2018).

The genes implicated in angiogenesis, metabolism, arterial tone control and erythropoiesis can be activated by hypoxia inducible factor-1 (Feng, Zhan & Ma, 2021), a transcription factor that is reactively produced when intracellular oxygen partial pressure decreases. HIF-1α and HIF-1β make up a combination of two proteins. They are both members of the family of polypeptides known as basic helix-loop-helix (Wu et al., 2019). The 826-amino-acid-long HIF-1α protein acts as a trans-transcriptional regulator of erythropoietin, lactate dehydrogenase, vascular endothelial growth factor and inducible nitric oxide synthase (Jiang et al., 2018). In a normal environment, HIF-1α has a low level, exists only in the cytoplasm and has a stable molecular structure which is not easily degraded. Its main function in the body is to promote vascular remodelling and improve collateral circulation. However, HIF-1α is extremely sensitive to hypoxia. After AMI, the hypoxia becomes serious with blood vessel stenosis. At this time, the level of HIF-1α increases rapidly, thus activating a variety of cytokines in the body, improving collateral circulation ability, vascular remodelling and the state of myocardial ischaemia and hypoxia (Li et al., 2021).

ESM-1 is a dermatan sulphate proteoglycan with numerous biological functions, and its synthesis increases in response to neovascularisation or endothelial cell damage. ESM-1 is primarily secreted by endothelial cells (Wei et al., 2021). Dikalova et al. (2020) showed that when cardiovascular abnormalities occur, the pro-inflammatory factors in vascular endothelial cells induce ESM-1 upregulation through protein kinase C/nuclear factor κB signalling pathway.

This study found that the occurrence of MACEs in patients indicated the presence of hypoxia and ischaemia, and the increased levels of HIF-1α, EMPs and ESM-1 provided a basis for the clinical prediction of MACEs in patients with AMI. The high expression of HIF-1α, EMPs and ESM-1 might be important predisposing factors for the occurrence of MACE in patients with AMI. Our study brings several novel aspects to the literature on AMI and MACE. The combined predictive value of serum levels of ESM-1, EMPs, and HIF-1α for MACE has not been extensively explored previously. The AUC of 0.931 for the combined biomarkers indicated their high diagnostic value, suggesting that this multi-marker approach can improve risk stratification for patients post-AMI. Additionally, the roles of these biomarkers in the pathophysiology of AMI are highlighted, offering insights into their mechanisms and potential as therapeutic targets. This comprehensive analysis contributes to further understanding of the disease and may inform future clinical strategies.

Conclusions

Patients with AMI have abnormally high levels of ESM-1, EMPs, and HIF-1α in their serum, all of which have been linked to the development of MACE. Together, these parameters have high sensitivity and specificity for early MACE detection. Given that this study was retrospective and all the patients were from our institution, the possibility of selection bias cannot be ruled out. Additional research is required to validate these findings. Further investigation and confirmation are also warranted because the precise mode of action is still unknown.

Supplemental Information