Abstract
It has been shown that thoracic aortic aneurysm and dissection (TAAD) could be a Mendelian trait caused by a single gene mutation. The LOX gene mutation leads to the development of human TAAD. The LOXL4 gene is a member of the lysyl oxidase gene family. We identified seven variants in the LOXL4 gene in 219 unrelated patients with TAAD by whole-exome sequencing (WES). To further investigate whether LOXL4 is a candidate causative gene for human TAAD, a Loxl4 knockout mouse was generated, and the mutant mice were treated by subcutaneous infusion of angiotensin II. We found that abrogation of Loxl4 did not induce a more severe thoracic or abdominal aortic aneurysm compared with the wild-type C57BL/6J mice. Our results suggest that LOXL4 may not play a major role in the development of angiotensin II-induced aortic aneurysm. The functional study using this animal model system is important for the evaluation of candidate genes of TAAD identified by WES.
Highlights
Aortic aneurysm (AA) is a degenerative condition that leads to vascular remodeling and luminal expansion of the aorta wall
In order to identify new candidate genes related to thoracic aortic aneurysm and dissection (TAAD), we pinpointed seven variants from eight patients in the LOXL4 gene of the Lysyl oxidase (LOX) gene family (Table 1)
The LOX family is essential to the biogenesis of connective tissue, which catalyzes the first step in the formation of crosslinks in collagens and elastin
Summary
Aortic aneurysm (AA) is a degenerative condition that leads to vascular remodeling and luminal expansion of the aorta wall. One of the most widely used mouse aortic aneurysmAA () models is the subcutaneous infusion of angiotensin II into Apoe –/– or C57BL/6J mice through osmotic pumps, which is a reliable and reproducible technique to induce both TAA and AAA [8]. This mouse model system has been used to study the candidate genes by ameliorating or enhancing angiotensin II-induced AAAs [9,10,11]. This study shows that Loxl abrogation did not exaggerate angiotensin II-induced thoracic or abdominal aortic aneurysm in mice by using the angiotensin II-induced TAA or AAA mouse model system
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