FRZB as a key molecule in abdominal aortic aneurysm progression affecting vascular integrity

• Published in: Bioscience reports Vol. 41; no. 1
• Main Authors: Oh, Chang-Kyu, Ko, Yeji, Park, Jeong Jun, Heo, Hye Jin, Kang, Junho, Kwon, Eun Jung, Kang, Ji Wan, Lee, Yoonsung, Myung, Kyungjae, Kang, Jin Mo, Ko, Dai Sik, Kim, Yun Hak
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd The Biochemical Society 29-01-2021; Portland Press Ltd
• Subjects: Abdomen; Aorta; Aortic aneurysms; Atherosclerosis; Bioinformatics; Biotechnology; Cardiovascular disease; Cardiovascular System & Vascular Biology; Cell interactions; Chromosome 1; Danio rerio; DNA microarrays; Elastin; Embryos; Extracellular matrix; Frizzled protein; Frizzled-related protein; Gene expression; Gene Expression & Regulation; Genes; Integrity; Mortality; Omics; Patients; Standardization; Vertebrates; Zebrafish; Germany; gene expression omnibus; zebrafish; FRZB; vascular integrity; abdominal aortic aneurysm; bioinformatics
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20203204

Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell-cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.