Abdominal aortic aneurysm (AAA) is defined as focal dilatation of the abdominal aorta, which is either 50% larger than the normal diameter, or characterized by permanent localized dilatation of the abdominal aorta when the diameter of the aorta exceeds 30 mm(1, 2, 12). AAA is one of the most important causes of morbidity and death in middle-aged and elderly people(3). Risk factors for AAA include advanced age, male, Caucasian race, disease, atherosclerotic disease and smoking, which are considered to be the main modifiable risk factor (5, 13, 14). Other potential risk factors include diabetes (DM), which has been shown to be negatively associated with AAA (15), higher height (16), and low fruits and vegetables intake (17). Acute rupture is the most dangerous clinical consequence of AAA progression. About 80% of related deaths in the United States are caused by acute rupture (6), and AAA pathological features include vascular smooth muscle cell apoptosis, inflammatory cell infiltration, loss of arterial wall integrity, increased oxidative stress and significant matrix degradation (7, 8), and aortic wall thinning caused by vascular smooth muscle cell (VSMCs) loss (18–20). There are many potential mechanisms for the pathogenesis of AAA, including inflammation, VSMCs apoptosis, ECM degradation and oxidative stress(8, 21, 22). Pro-inflammatory cytokines such as IL-1 β, IL-10, IL-6, IL-13, TNF-α and interferon-γ in diseased aortic walls promote the development of abdominal aortic aneurysms by regulating the secretion of matrix metalloproteinases(23). The prevalence of AAA is 4 to 7 per cent in men and 1 to 2 per cent in women over the age of 65, which may only be due to the protection of estrogen, as women are no longer protected against AAA after menopause(24). However, women had a higher incidence of ruptured aneurysms after surgical repair (25, 26). AAA is usually asymptomatic and does not seem to pass routine screening, which is accidentally found in imaging tests used to assess other health problems (27–29). At a later stage, ruptured abdominal aorta can lead to high mortality. Therefore, it is particularly urgent to explore the molecular mechanism of AAA and improve the treatment level of AAA patients.
Exosomes are extracellular vesicles with diameters between 30 and 100 nanometers(30). These nano-sized vesicles are produced in poly cystic bodies and are released by cells through the fusion of these compartments with the plasma membrane. They are important components of intercellular communication through the transmission of intracellular components, such as DNA, RNA and proteins(31). Exosomes can be released by various types of cells, including immune cells and tumor cells. Tumor cells secrete more exosomes than normal cells (32). The exosome secreted can be ingested by nearby or distant cells. In the past decade, exosomes have become the focus of research. It is worth noting that exosomes from tumors play an important role in the occurrence and development of tumors. For example, gastric cancer (GC)-derived exosomes promote tumor cell proliferation by activating phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) pathways(33). (HCC)-derived exosomes of primary hepatocellular carcinoma regulate the adhesion of HCC cells in circulation by transmitting SMAD family member 3 (SMAD3), thus promoting tumor metastasis(34). Exoskeletons derived from (HNSCC) in head and neck squamous cell carcinoma can promote angiogenesis by reprogramming receptor endothelial cells(34). In addition, exosomes were found in various body fluids such as saliva, blood and urine (35, 36). The accessibility of exosomes in almost all body fluids shows their potential as potential non-invasive biomarkers for different types of cancer. Most importantly, what is closely related to this study is the involvement of macrophages in the pathogenesis of AAA.
Long non-coding RNA (LncRNAs) is a transcript whose length is larger than 200nt and does not have the ability to encode protein. LncRNAs in vitro is not affected by ribonuclease-mediated degradation and stably exists in body fluids. LncRNAs regulates protein expression by epigenetic, transcriptional and post-translational levels (37–39). One of the most well-known mechanisms of lncRNAs is their role as competitive endogenous (Ce) RNA(40). To identify the possible function of lncRNAs adjacent genes are to explore the function of lncRNAs. It has been found that a large number of lincRNAs and lncRNAs, with enhancer-like functions are related to trans-transcriptional regulation, translation control, splicing regulation and other post-transcriptional regulation. There is more and more evidence that lncRNA is related to the occurrence and development of cancer by directly or indirectly interfering with gene expression. A new lncRNA long gene non-protein coding RNA473 (LINC00473) can promote cell proliferation and inhibit apoptosis in a variety of cancers, such as breast cancer (41), lung cancer(42), nephroblastoma(43), cervical cancer(44) and so on. In other words, LINC00473 seems to play a general inhibitory role in cancer cell apoptosis. LncRNAs has been identified as a new regulator of cancer cell proliferation and apoptosis (45–47). However, the role of most lncRNAs in AAA is not clear, and apoptosis occurs in VSMCs during this process. LINC00473 has been shown to promote cell proliferation but inhibit apoptosis in many cancers (41, 42). Therefore, more and more attention has been paid to the field of lncRNAs exocrine research. So far, a variety of lncRNAs have been reported to be involved in regulating the development of AAA. For example, lncRNAH19 promotes AAA formation and vascular inflammation by regulating the expression of IL-6 (48). In addition, LINC00265 is thought to promote AAA inflammation by isolating let-7a. H19 is considered to be an important inducer of AAA (49). In mouse AAA model, silencing PVT1 resulted in inhibition of VSMCs apoptosis. In addition, growth inhibition specificity 5 (Gas5) was found to promote apoptosis in VSMC and promote the formation of AAA(50). Hypoxia inducible factor 1 (HIF-1) and α-AS1 are the first reported LncRNA(7) associated with thoracic aortic aneurysms(51) identified 3688 differentially expressed lncRNA,AC005224.4 and SENP3EIF4A1 involved in signal transduction, protein amino acid phosphorylation and immune response, and ZNRD1-AS1 involved in transcription, development and cell differentiation. It is reported that CDKN2B-AS1 interacts with cytokinesis regulatory proteins 1 and-2, resulting in epigenetic silencing of CDKN2B(52). The Cerna hypothesis proposed by Tay et al. (53) suggests that pseudogenes, lncRNAs, circular RNAs and mRNAs may weaken the activity of tiny (MI) RNA through isolation, thus up-regulating the expression of miRNA target genes. Franco-Zorrilla et al(53). Reported for the first time that non-coding RNA interferon-β promoter stimulator 1 promotes phosphate metabolism of (Pho)-2 protein in plants by isolating miR-399 and preventing it from inhibiting PHO2mRNA stability and translation. In this study, we generally understand that exocrine lncRNAs plays an important role in vivo and plays an important role in the occurrence and development of AAA, but because this study is not in-depth, and the number of samples is small, the result is single, the current stage of work is to further in-depth and specific study of the mechanism of action of a single lncRNA, in order to achieve the purpose of clinical application. Unfortunately, due to the small number of samples in this study and the lack of basic experiments, the results are relatively preliminary. The next stage is to add basic experiments to further verify our conclusions.