Abstract
Thoracic Aortic Aneurysm (TAA) is characterized by the dilation of the aorta and is fatal if not diagnosed and treated appropriately. The underlying genetic mechanisms have not been completely delineated, so better knowledge of the physiopathology of TAAs is needed to improve detection and therapy. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and are known to be involved in cardiovascular diseases (CVDs). The current study aimed to identify miRNAs that can be used as possible biomarkers for the early diagnosis of patients with ascending TAAs (ATAAs). MiRNA expression was profiled by NanoString nCounter technology using 12 samples including tissue and pre- and post-surgical plasma from ATAA patients. Four miRNAs were selected and further validated by real time polymerase chain reaction (RT-PCR) in 22 plasma samples from which three miRNAs (hsa-miR140-5p, hsa-miR-191-5p and hsa-miR-214-3p) showed significant expression level differences between the two types of plasma samples. Further analyses of the corresponding predicted target genes by these miRNAs, revealed two genes (Myotubularin-related protein 4 (MTMR4) and Phosphatase 1 catalytic subunit β (PPP1CB)) whose expression was inversely correlated with the expression of their respective miRNAs. Overall, in this pilot study, we identified three miRNAs that might serve as potential biomarkers and therapeutic targets in ATAA.
Highlights
Thoracic aortic aneurysm (TAA) may be defined as a localized or diffuse dilatation of the aorta to at least a 50 percent increase in diameter compared with the expected normal diameter
Using the gene expression profile obtained from the Nanostring data, a total of 80 miRNAs were detected in eight plasma samples and they were confirmed in four tissue samples
The detection of the circulating levels of the miRNAs may be dependent on the diseased aortic tissue samples either by originating or being enriched in this particular tissue. Eight of these miRNAs, showed significant difference (P≤0.001) in their expression levels between blood samples before (BB) and BA plasma samples and in all cases the expression was lower in BB samples while the levels were much higher in the tissue samples (Table 4)
Summary
Thoracic aortic aneurysm (TAA) may be defined as a localized or diffuse dilatation of the aorta to at least a 50 percent increase in diameter compared with the expected normal diameter. The aortic root, ascending aorta, aortic arch, or descending aorta may be affected and are classified [1]. Sixty percent of TAAs involve the aortic root and/or ascending aorta, 40% involve the descending aorta, 10% involve the arch, and 10% involve the thoracoabdominal aorta [2]. Ascending TAAs (ATAAs) most often result from cystic medial degeneration, which appears histologically as smooth muscle cell dropout and elastic fiber degeneration. Medial degeneration leads to weakening of the aortic wall, which in turn results in aortic dilatation and aneurysm formation [2]. It is more often associated with a genetic predisposition that can be familial [4] or related to defined genetic disorders such as Marfan syndrome
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