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Tissue‐ and Plasma‐Specific MicroRNA Signatures for Atherosclerotic Abdominal Aortic Aneurysm

2012; Wiley; Volume: 1; Issue: 5 Linguagem: Inglês

10.1161/jaha.112.000745

2047-9980

Keiwa Kin, Shigeru Miyagawa, Satsuki Fukushima, Yukitoshi Shirakawa, Kei Torikai, Kazuo Shimamura, Takashi Daimon, Yukio Kawahara, Toru Kuratani, Yoshiki Sawa,

MicroRNA in disease regulation

Background 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. Micro RNA s play a fundamental role in atherosclerosis, and atherosclerotic coronary artery disease is characterized by tissue‐ and plasma‐specific micro RNA signatures. However, little is known about micro RNA s involved in AAA pathology. This study examined tissue and plasma micro RNA s specifically associated with AAA . Methods and Results 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. Micro RNA expression was assessed by high‐throughput micro RNA arrays and validated by real‐time polymerase chain reaction for individual micro RNA s that showed significant expression differences in the initial screening. Micro RNA s 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 micro RNA s, 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). Conclusions The expression of some micro RNA s was specifically upregulated in AAA tissue, warranting further studies on the micro RNA function in AAA pathogenesis and on the possibility of using a micro RNA biomarker for AAA diagnosis.