The role and mechanism of epidermal growth factor receptor in hemodynamic induction of abdominal aortic aneurysm formation

Abstract

Background: Abdominal aortic aneurysm (AAA) is a serious threat to human health, and in the event of aneurysm rupture, the rates of disability and mortality are high. At present, the treatment of AAA mainly includes craniotomy and endovascular therapy. With advances in technology, although the safety of the treatment is improving, there is still a risk associated with surgery. Therefore, the exploration of non-invasive treatment options for aneurysms is worthwhile. The etiology of aneurysms must be investigated to identify the target of non-invasive treatment.

Methods: In the experimental group, bilateral common carotid arteries were ligated, while in the control group, bilateral common carotid arteries were exposed. After 5 days, the rabbits were sacrificed, and the hearts were perfused with normal saline. Smooth muscle cells (SMCs) of abdominal aorta were isolated by enzyme digestion. Total RNA was extracted from SMC samples and detected using an Agilent Rabbit 4×44K Gene Expression Microarray. Then, some genes were selected and real-time polymerase chain reaction (RT-PCR) was conducted to verify the credibility of the chip results. Finally, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. The transcriptome contained in the identified differentially expressed gene (DEG) was analyzed.

Results: Microarray revealed 947 DEGs, of which 617 genes were increased and 330 genes were decreased in the experimental group compared with the control group. The microchips of PTHLH, ENPP1, IGF1, and others were selected to verify the altered genes by PCR.

Conclusions: The gene expression of rabbit abdominal aorta SMCs was significantly changed under high blood flow load. Through data analysis, it was found that some specific genes and transcription factors may play an important role in hemodynamically-induced vascular remodeling.

Keywords: Hemodynamics; abdominal aortic aneurysm (AAA); gene microarray; smooth muscle cells (SMCs); vascular remodeling.

Figure 1

Basilar artery flow velocity before and after modeling [(A) flow velocity before modeling; (B) flow rate 5 days after modeling].

Figure 2

Comparison of basilar artery diameter between the control group and the experimental group. **, P<0.01.

Figure 3

Comparative analysis of differential gene expression. Red: up-regulated gene; green: down-regulated gene; blue: non-regulatory genes; black: negative gene expression.

Figure 4

Abdominal aorta was stained with IGF1 and TNF-α immunohistochemistry.

Figure 5

PPI network correlation analysis results. PPI, protein-protein interaction.