The pathogenesis shared between abdominal aortic aneurysms and intracranial aneurysms: a microarray analysis
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Abdominal aortic aneurysms (AAAs) and intracranial saccular aneurysms (IAs) are the most common types of aneurysms. This study was to investigate the common pathogenesis shared between these two kinds of aneurysms. We collected 12 IAs samples and 12 control arteries from the Beijing Tiantan Hospital and performed microarray analysis. In addition, we utilized the microarray datasets of IAs and AAAs from the Gene Expression Omnibus (GEO), in combination with our microarray results, to generate messenger RNA expression profiles for both AAAs and IAs in our study. Functional exploration and protein–protein interaction (PPI) analysis were performed. A total of 727 common genes were differentially expressed (404 was upregulated; 323 was downregulated) for both AAAs and IAs. The GO and pathway analyses showed that the common dysregulated genes were mainly enriched in vascular smooth muscle contraction, muscle contraction, immune response, defense response, cell activation, IL-6 signaling and chemokine signaling pathways, etc. The further protein–protein analysis identified 35 hub nodes, including TNF, IL6, MAPK13, and CCL5. These hub node genes were enriched in inflammatory response, positive regulation of IL-6 production, chemokine signaling pathway, and T/B cell receptor signaling pathway. Our study will gain new insight into the molecular mechanisms for the pathogenesis of both types of aneurysms and provide new therapeutic targets for the patients harboring AAAs and IAs.
KeywordsAbdominal aortic aneurysms Intracranial aneurysms Microarray Gene ontology Pathway analysis
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
This study was approved by the Ethics Committee of the Department of Medicine, Beijing Tiantan Hospital, Capital Medical University (KY2011-002-02) and the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants who were included in the study.
- 3.Humphrey JD, Taylor CA (2008) Intracranial and abdominal aortic aneurysms: similarities, differences, and need for a new class of computational models. Annu Rev Biomed Eng 10:221–246. https://doi.org/10.1146/annurev.bioeng.10.061807.160439 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Pera J, Korostynski M, Krzyszkowski T, Czopek J, Slowik A, Dziedzic T, Piechota M, Stachura K, Moskala M, Przewlocki R, Szczudlik A (2010) Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation? Stroke 41:224–231. https://doi.org/10.1161/STROKEAHA.109.562009 CrossRefPubMedGoogle Scholar
- 12.Li H, Yue H, Hao Y, Li H, Wang S, Yu L, Zhang D, Cao Y, Zhao J (2016) Expression profile of long noncoding RNAs in human cerebral aneurysms: a microarray analysis. J Neurosurg:1–8. https://doi.org/10.3171/2016.9.JNS16839
- 13.Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80. https://doi.org/10.1186/gb-2004-5-10-r80 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Leek JT (2014) svaseq: removing batch effects and other unwanted noise from sequencing data. Nucleic Acids Res 42. https://doi.org/10.1093/nar/gku864
- 20.Hinterseher I, Schworer CM, Lillvis JH, Stahl E, Erdman R, Gatalica Z, Tromp G, Kuivaniemi H (2015) Immunohistochemical analysis of the natural killer cell cytotoxicity pathway in human abdominal aortic aneurysms. Int J Mol Sci 16:11196–11212. https://doi.org/10.3390/ijms160511196 CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Liao M, Xu J, Clair AJ, Ehrman B, Graham LM, Eagleton MJ (2012) Local and systemic alterations in signal transducers and activators of transcription (STAT) associated with human abdominal aortic aneurysms. J Surg Res 176:321–328. https://doi.org/10.1016/j.jss.2011.05.041 CrossRefPubMedGoogle Scholar
- 23.Lindeman JH, Abdul-Hussien H, Schaapherder AF, Van Bockel JH, Von der Thusen JH, Roelen DL, Kleemann R (2008) Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm. Clin Sci (Lond) 114:687–697. https://doi.org/10.1042/CS20070352 CrossRefGoogle Scholar
- 24.Harrison SC, Smith AJ, Jones GT, Swerdlow DI, Rampuri R, Bown MJ, Aneurysm C, Folkersen L, Baas AF, de Borst GJ, Blankensteijn JD, Price JF, van der Graaf Y, McLachlan S, Agu O, Hofman A, Uitterlinden AG, Franco-Cereceda A, Ruigrok YM, van't Hof FN, Powell JT, van Rij AM, Casas JP, Eriksson P, Holmes MV, Asselbergs FW, Hingorani AD, Humphries SE (2013) Interleukin-6 receptor pathways in abdominal aortic aneurysm. Eur Heart J 34:3707–3716. https://doi.org/10.1093/eurheartj/ehs354 CrossRefPubMedGoogle Scholar
- 25.Sawyer DM, Pace LA, Pascale CL, Kutchin AC, O'Neill BE, Starke RM, Dumont AS (2016) Lymphocytes influence intracranial aneurysm formation and rupture: role of extracellular matrix remodeling and phenotypic modulation of vascular smooth muscle cells. J Neuroinflammation 13:185. https://doi.org/10.1186/s12974-016-0654-z CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Yurtsever Z, Scheaffer SM, Romero AG, Holtzman MJ, Brett TJ (2015) The crystal structure of phosphorylated MAPK13 reveals common structural features and differences in p38 MAPK family activation. Acta Crystallogr D Biol Crystallogr 71:790–799. https://doi.org/10.1107/S1399004715001212 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Wang C, Chang Q, Sun X, Qian X, Liu P, Pei H, Guo X, Liu W (2015) Angiotensin II induces an increase in matrix metalloproteinase 2 expression in aortic smooth muscle cells of ascending thoracic aortic aneurysms through JNK, ERK1/2, and p38 MAPK activation. J Cardiovasc Pharmacol 66:285–293. https://doi.org/10.1097/FJC.0000000000000276 CrossRefPubMedGoogle Scholar
- 30.Weinsheimer S, Lenk GM, van der Voet M, Land S, Ronkainen A, Alafuzoff I, Kuivaniemi H, Tromp G (2007) Integration of expression profiles and genetic mapping data to identify candidate genes in intracranial aneurysm. Physiol Genomics 32:45–57. https://doi.org/10.1152/physiolgenomics.00015.2007 CrossRefPubMedGoogle Scholar