Update on abdominal aortic aneurysm research: from clinical to genetic studies

Abstract

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person's risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks.

Figure 1

Survival analysis for patients after a ruptured abdominal aortic aneurysm (rAAA), elective open repair (eAAA), or elective endovascular repair (EVAR). Kaplan-Meier curves were generated with the indicated numbers of patients at risk. Reproduced with permission from [26].

Figure 2

Economic analysis of internal iliac artery embolizations. Coil embolization (COIL) and Amplatzer Vascular Plug embolization (PLUG) charges, operating room charges, and total hospital charges for internal iliac artery embolizations performed prior to endovascular aneurysm repair for the time period from 2004 to 2010 (standardized to 2011 dollars). Reproduced with permission from [31].

Figure 3

Seroprevalences for Borrelia burgdorferi sensu lato antibodies in different risk groups in Germany. Only studies with both ELISA and immunoblotting data were included. AAA, abdominal aortic aneurysm; PAD, peripheral artery disease. For details, see [70]. Reproduced with permission from [70].

Figure 4

Heat map of the 57 differentially expressed genes found in two independent microarray studies for AAA. The heat map was produced by hierarchical clustering of the probeset data. Probesets for genes are represented by rows with the gene dendrogram at left. There are 61 probesets represented since there are redundant probesets on the Affymetrix microarray for some genes, for example, CXCR4, which is the gene represented by three lines at the bottom. Gene symbols and gene IDs on the right (found at http://www.ncbi.nlm.nih.gov/). Samples (4 AAA samples and 4 controls) are represented by columns. Green color indicates decreased expression in AAA and red color indicates increased expression in AAA.

Figure 5

A Network of miRNAs, miR-133a, miR-133b, miR-331-3p, and miR-204, and their target genes. Each miRNA is predicted to regulate a large number of target genes (mRNAs). Bioinformatic analysis predicted that 222 genes with upregulated expression in AAA based on a prior microarray study [81] were targets of miR-133a, miR-133b, miR-331, or miR-204. The predicted minimum free energy of the miRNA and target mRNA hybridization from the program RNAhybrid version 2.1.is shown by the line and node color. Black lines for YTHFD3 indicate that the 3′UTR sequence was not available from Ensembl BioMart, and the minimum free energy was not calculated. miR-30c-2* was not included because it is a miRNA* strand that is usually degraded and therefore nonfunctional. The figure is reproduced from [84].