Abstract
Thoracic aortic aneurysm (TAA) can lead to fatal complications such as aortic dissection. Since aneurysm dimension poorly predicts dissection risk, microRNAs (miRNAs) may be useful to diagnose or risk stratify TAA patients. We aim to identify miRNAs associated with TAA pathogenesis and that are possibly able to improve TAA diagnosis. MiRNA microarray experiments of aortic media tissue samples from 19 TAA patients and 19 controls allowed identifying 232 differentially expressed miRNAs. Using interaction networks between these miRNAs and 690 genes associated with TAA, we identified miR-574-5p as a potential contributor of TAA pathogenesis. Interestingly, miR-574-5p was significantly down-regulated in the TAA tissue compared to the controls, but was up-regulated in serum samples from a separate group of 28 TAA patients compared to 20 controls (p < 0.001). MiR-574-5p serum levels discriminated TAA patients from controls with an area under the receiver operating characteristic curve of 0.87. In the Fbn1C1041G/+ mouse model, miR-574-5p was down-regulated in aortic tissue compared to wild-type (p < 0.05), and up-regulated in plasma extracellular vesicles from Fbn1C1041G/+ mice compared to wild-type mice (p < 0.05). Furthermore, in vascular smooth muscle cells, angiotensin II appears to induce miR-574-5p secretion in extracellular vesicles. In conclusion, miR-574-5p is associated with TAA pathogenesis and may help in diagnosing this disease.
Highlights
Thoracic aortic aneurysm (TAA) is a life-threatening disease with an incidence of approximately 10/100,000 population [1]
Whereas monogenic etiologies are often observed in young patients [4] as for instance Marfan syndrome caused by mutation of the FBN1 gene encoding the protein fibrillin-1 [5] or Loeys-Dietz syndrome, due to mutations in TGF-β related genes such as TGFBR1 or TGFBR2 amongst others, older patients may show a degenerative form of aneurysm and the presence of a bicuspid aortic valve promotes TAA [6]
The “tissue” and “serum” cohorts were composed of TAA patients and controls without aortic aneurysm
Summary
Thoracic aortic aneurysm (TAA) is a life-threatening disease with an incidence of approximately 10/100,000 population [1]. Patients with TAA are at higher risk to develop severe aortic complications as intramural hematoma, dissection, or rupture of the aorta. To prevent such complications, patients require regular follow-up and sometimes prophylactic aortic surgery [2]. Monogenic alterations have been identified that induce or foster TAA, no pathogenic variant can be identified for 70% of patients with familial TAA [11] Physiological mechanisms such as the renin-angiotensin system and the TGF-β pathway have been implicated in TAA [12] and in VSMC phenotypic switch [13]. The high number of genes involved and the numerous mechanisms thought to be involved in TAA formation and progression support the complexity of this disease, which is yet to be fully understood [15]
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