• 2018-07
  • 2019-04
  • br Materials and methods br Conflict


    Materials and methods
    Conflict of interest statement
    Acknowledgements This work was supported by the National Natural Science Foundation of China (No: 31100781); the Natural Science Foundation of Hebei Province, PR China (No: C2011206040); and the Department of Health of Hebei Province (No: 20090313).
    Introduction Abdominal aortic aneurysm (AAA) is a permanent, localized dilation of the aorta, occurring in nearly 9% of adults older than 65 years of age in the United States, leading to approximately 15,000 annual deaths following rupture [1,2]. Despite decades of research into AAA, there remains a paucity of fundamental understanding of the mechanisms that cause it or factors that block its progression. Thus, a critical step in the development of novel pharmacologic therapies for AAA is elucidation of the molecular basis for the disease. Many researchers have established that vascular smooth muscle cells (VSMCs) play an important role in the development of arterial diseases because their function is to remodel the vascular wall. Studies have shown that there was phenotypic switching and apoptosis of VSMCs during the formation of aortic aneurysm [[3], [4], [5], [6]]. Previously, we established that the p38 mitogen-activated protein kinase (MAPK) pathway is involved in the process of phenotypic switching in VSMCs [5]. However, the mechanisms responsible for modulation of the p38 MAPK pathway and apoptosis of VSMCs remains unclear. The classic function of aminoacyl-tRNA synthetases (AARSs) is synthesis of proteins which specifically recognize the side chains and tRNAs of amino acids, catalyzing the binding of specific amino acids to specific tRNAs. This ensures that the genetic information carried by individual mRNA strands is accurate, reflected in the amino everything sequence of that protein [7]. Recently, a number of AARSs have been recognized as having involvement in other functions in addition to protein synthesis, such as immunity, angiogenesis, transcriptional regulation and apoptosis [8,9]. Isoleucyl-tRNA synthetase (Iars), a member of the amino acid tRNA transport synthetase family which is encoded by the IARS gene [10], has been reported to be responsible for hypertrophic cardiomyopathy and inhibit angiogenesis [11,12]. Our search and analysis of the GEO database (GLP10787) found that mRNA expression of IARS in the aorta of patients with abdominal aortic aneurysm (AAA) was significantly greater than that of non-AAA patients (Supplementary Fig. 1). An imbalance in aortic medial damage and repair is an important characteristic of aortic disease. Whether Iars can affect the occurrence of AAA by inhibiting the repair process of the aortic wall has not been reported. In a preliminary experiment we confirmed that the protein expression of Iars was greater in tissues suffering AAA.
    Materials and methods
    Discussion Abdominal aortic aneurysm is a disease that is seriously life-threatening. However, the cause of the disease has not yet been fully elucidated. Therefore, the study of possible mechanisms of pathogenesis is of great importance for future prevention, diagnosis and treatment of the disease. Studies have shown that aortic medial degeneration is the principal pathological feature of aortic aneurysm [16,17]. In this study we discovered a possible mechanism underlying AAA. Isoleucyt-tRNA synthetase can induce apoptosis and phenotypic switching in VSMCs during AAA formation via the PI3K and p38 MAPK signaling pathways, respectively. Cells respond to changes in their microenvironment by modifying many cellular programs, including cell survival, proliferation, differentiation, metabolism, interactions with other cells and numerous homeostatic loops. VSMCs switch their phenotype, from contractile to synthetic, in response to these microenvironmental cues in a process known as phenotypic switching. The release of various stress factors such as Ang II, oxidative stress and inflammatory factors during the pathogenesis of aortic aneurysm is significantly elevated, leading to VSMC dysfunction [18,19]. We have demonstrated that the expression of OPN and Bax was considerably greater, and SM22α lower, in the medial layer of specimens taken from tissues exhibiting AAA than did nonpathological controls, thereby suggesting that phenotypic switching and apoptosis had taken place. Our finding is consistent with previous research [20,21] that reported phenotypic switching and apoptosis of VSMCs was observed in aortic aneurysm tissues, but the precise mechanisms of which were unclear.