Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm.
Atherosclerotic abdominal aortic aneurysm (AAA) is a progressive, gradual aortic rupture that results in death in the absence of surgical intervention. Key factors that regulate initiation and progression of AAA are unknown, making targeted interventions difficult. MicroRNAs play a fundamental role in atherosclerosis, and atherosclerotic coronary artery disease is characterized by tissue- and plasma-specific microRNA signatures. However, little is known about microRNAs involved in AAA pathology. This study examined tissue and plasma microRNAs specifically associated with AAA. AAA and normal wall tissues were sampled from patients undergoing AAA repair (n=13; mean age, 68±6 years) and aortic valve replacement surgery (n=7; mean age, 66±4 years), respectively. MicroRNA expression was assessed by high-throughput microRNA arrays and validated by real-time polymerase chain reaction for individual microRNAs that showed significant expression differences in the initial screening. MicroRNAs related to fibrosis (miR-29b), inflammation (miR-124a, miR-146a, miR-155, and miR-223), and endothelium (miR-126, let-7 family members, and miR-21) were significantly upregulated in AAA tissue. Significant negative correlations were seen in expression levels of monocyte chemoattractant protein-1 and miR-124a, -146a, and -223; tumor necrosis factor-α and miR-126 and -223; and transforming growth factor-β and miR-146a. Expression of microRNAs, such as miR-29b, miR-124a, miR-155, and miR-223, that were upregulated in AAA tissue was significantly reduced in plasma of patients with AAA (n=23; mean age, 72±9 years) compared to healthy controls (n=12; mean age, 51±11 years) and patients with coronary artery disease (n=17; mean age, 71±9 years). The expression of some microRNAs was specifically upregulated in AAA tissue, warranting further studies on the microRNA function in AAA pathogenesis and on the possibility of using a microRNA biomarker for AAA diagnosis.