Popularity of research can be measured by the number of publications in a field [21,22]. From 2012 to 2022, molecular imaging research on AS biomarkers have undergone a stable development period accompanied by a wave-like uplift trend.At the same time, the number of academic papers published had almost doubled, which indicated that more investigators are focused on the domain.
The United States was the leading country and institution in terms of publications in this field,Asian countries (China, Japan, and Turkey), European countries (Germany, UK, Italy, Switzerland, Netherlands), and Oceanian countries (Australia) are the main drivers of research related to atherosclerosis biomarkers.All the top 10 contributing institutions are located in the United States, which means that American researchers maintain a dominant position in publications in this field. However, lower centrality suggested that they have less influence on each other and less global cooperation. Strengthen the capacity of Asian journals and global cooperation is an urgent problem so that countries can deliver high-quality scientific output and disseminate knowledge in this field.
In addition, Atherosclerosis, PLOS ONE, Journal of the American Heart Association, Scientific Reports, International Journal of Cardiology, and Atherosclerosis are considered core journals in the field due to their publication volume and high co-citation rates.
Co-occurrence analysis of keywords clarifies the research hot topics in the study, and clustering can display the knowledge structure. Furthermore, overlay view and citation burst detection are two of the central methods for tracing the evolution of science [23].Studies on atherosclerosis biomarkers have mainly focused on the following four aspects: disease type (atherosclerosis, cardiovascular disease, coronary artery disease, coronary heart disease, myocardial infarction, metabolic syndrome), pathological links (inflammation, expression, oxidative stress, insulin resistance, arteriosclerosis, endothelial dysfunction, pulse wave velocity), and detection indicators were (C-reactive protein, intimal media thickness, low density lipoprotein). Among them, coronary heart disease, arteriosclerosis, inflammation, pulse wave velocity, C-reactive protein, and intimal media thickness are the research hotspots in this field. Studies on atherosclerosis biomarkers from 2012 to 2015 focused on arterial disease, subtilis protein invertase, lymphocyte ratio, high-density lipoprotein, and hypersensitive cardiac troponin. After 2014, studies focused on noncoding RNA and the atherosclerosis index, which showed that, based on atherosclerosis biomarkers, The researchers have carried out a large range of explorations of in the disease, pathological mechanism, examination indicators, etc., to provide a better reference for the search for atherosclerosis biomarkers.
In terms of research hotspots, the research hotspots from 2012 to 2016 mainly focused on C-reactive protein, quantitative, in vivo, unstable angina pectoris, metabolic syndrome, and apolipoprotein E deficiency mice. After 2019, attention will be given to atherosclerotic cardiovascular diseases, extracellular vesicles, monocytes, long noncoding RNAs, neutrophil external trapping nets,etc. which indicates that researchers have tried to explore atherosclerosis biomarkers from multiple approaches and indicators. Here,we list some representative examples:
(1) Non-coding RNAs
Non-coding RNAs(ncRNAs) are RNAs that do not encode proteinsand mainly include microRNAs(miRNAs), long noncoding RNAs(LncRNAs) and circular RNAs (circRNAs). Many studies have shown that NcRNAs can be used as markers to predict and evaluate the prognosis of cardiovascular diseases.The increased expression of miR-126 in patients with coronary heart disease indicates that miR-126 is positively correlated with the risk of myocardial infarction, and the expression levels of miR-197 and miR-223 are negatively correlated with the incidence of coronary heart disease[24]. Leistner[25] confirmed through optical coherence tomography that the elevations of miR-126, miR-145, miR-155 and miR-29b in vivo were correlated with the degree of coronary artery stenosis, which played a certain role in determining the severity of coronary atherosclerosis.
(2) Extracellular vesicles
Extracellular vesicles (EVs) are lipid bilayer extracellular vesicles with a diameter of 30~1000 nm. They are divided into exosomes, microvesicles and apoptotic bodies according to their size, biomarkers and pathogenesis. Extracellular vesicles are involved in the occurrence and progression of cardiovascular disease in different ways, and elevated levels of microvesicles have been reported in subclinical atherosclerosis[26] and MACE[27] patients, as well as individuals with cardiometabolic risk factors[28]. A large amount of evidence has shown that atherosclerotic plaques contain high levels of EVs[29], and EVs are significant from the early stage by influencing the function of endothelial cells and the accumulation of lipids and leukocytes in the intima to the late stage by participating in plaque stability and thrombosis [30].
(3) External neutrophil trap
Neutrophil extracellular traps are complexes released by neutrophils into the periphery to function. Doring[31] clarified a mechanism for the pathogenesis of atherosclerosis driven by neutrophil extracellular traps, that is, plasmacytoid dendritic cells (pDCs) in the blood vessel wall are isolated from autologous DNA (presumably DNA carried by neutrophil extracellular traps). However, it is also possible that autoDNA from dying cells) and a complex of neutrophilic granulocyte proteins (such as antimicrobial peptides) stimulate a strong type I interferon response that promotes atherosclerosis. However, PLX3397 antibody treatment did not produce the same proatherogenic effect in mice lacking type I interferon receptors [31]. In addition, neutrophil extracellular traps can directly activate and damage endothelial cells, leading to their dysfunction as a starting point for atherosclerosis [32,33], while pretreatment with chloramidine (an inhibitor of PAD4) can reduce the formation of neutrophil extracellular traps in atherosclerotic mice. Thus the size of atherosclerotic lesions are reduced. [34,35].
It can be seen from the above that the research on AS biomarkers has obtained many achievements, and early diagnosis,risk predictions, and targeted precise treatment will be the directions in the future. However, most of the studies are still in an initial stage,due to the lack of clinical validation, and their conversion to the clinic needs to be verified by further studies.
Although this current research was performed by two bibliometric applications juxtaposed with one online scientometric platform, which provided more thorough and objective outcomes, there are still some limitations. First l, only articles from the Web of Science database were included; certain significant research in other databases such as Google Scholar and Scopus or in other languages might be neglected. Hence, the integrity of the data is insufficient, and the report findings may be influenced. Nevertheless, SCIE, as the world’s most powerful database in the medical field is the most commonly used database in scientometric analysis, and a great majority of scientific articles are published in English. Therefore, the results of this study still have some referential significance. Second, in general, there is a time delay in citations of high-quality papers published recently. In addition, some keywords and institutions’ names have different expressions that may have an impact on the clustering analysis even after our manual inspection procedures. Last but not least, similar to other bibliometric reports [36],this study may ignore the abundant semantic information contained in the sample literature, and the perspective of analyzing the evolution of this field is relatively singular.