Tissue microRNA expression in aortic aneurysm dissection

Abstract

Abstract Background Dissection and other complications of ascending aortic aneurysms are potentially life-threatening. Several factors may be implicated in aneurysm progression and dissection. The role of tissue microRNAs may be of interest. Purpose To examine how serum biomarkers and tissue expression of microRNAs are associated with thoracic aortic aneurysms and dissection. Methods We compared three groups of patients; 21 patients with aneurysm of the aortic root, ascending aorta or aortic arch undergoing scheduled repair, 11 patients with acute Stanford type A aortic dissection who underwent emergency surgery and 18 patients with normal aortic diameter undergoing other cardiac surgery (control group). Prior to surgery, peripheral blood samples were obtained from patients, to assess osteoprotegerin and adiponectin levels with the ELISA method. Tissue samples from ascending aortic wall were obtained from patients during surgery. Following appropriate storage and homogenization, tissue Matrix Metalloproteinases (MMPs) 2 and 9 were measured with the ELISA method, while tissue microRNAs 29 and 195 were measured using qrtPCR, after RNA extraction. Results There was no significant difference among control, aneurysm and dissection groups in terms of age (62±10 years vs 66±12 years vs 59±12 years, p=0.052), gender distribution (77.8% male vs 81% male vs 90% male, p=0.28) or BMI (28.51±2.92 kg/m2 vs 25.72±3.09 kg/m2 vs 27.02±3.2 kg/m2, p=0.76). There was also no difference among control, aneurysm and dissection groups regarding hypertension (72% vs 62% vs 73%, p=0.73), diabetes mellitus (22% vs 19% vs 36%, p=0.54), smoking (44% vs 29% vs 46%, p=0.09) or dyslipidemia (78% vs 43% vs 55%, p=0.08). The groups of control subjects, aneurysms and dissections did not differ in osteoprotegerin [44 (28, 52) pmol/l vs 31 (28, 37) pmol/l vs 45 (24, 71) pmol/l, p=0.17], adiponectin [6,65 (2,39, 9,79) μg/ml vs 5,28 (2,34, 6,98) μg/ml vs 4,13 (2,49, 7,52) μg/ml, p=0.43], tissue MMP2 [0.97 (0.42, 27.66) ng/ml vs 9.12 (1.72, 61.49) ng/ml vs 2.51 (0.22, 235.72) ng/ml, p=0.34] and tissue MMP9 levels [0.96 (0.29, 8.56) ng/ml vs 10.31 (1.18, 25.58) ng/ml vs 2.76 (0.63, 54.83) ng/ml, p=0.09] (Figure 1). Importantly, tissue expression of mir29 was 2.11-fold higher in the dissection group (p=0.001) and 2.99-fold higher in the aneurysm group (p<0.001) compared to the control group. Tissue expression of mir195 was 2.72-fold higher in the dissection group (p<0.001) and 2.00-fold lower in the aneurysm group (p=0.08) compared to the control group (Figure 2). Conclusions These findings highlight the role of epigenetic modifications through altered microRNA tissue expression in aortic wall synthesis, extracellular matrix degradation and progress of aneurysm formation and dissection. The exact role of microRNA expression in aortic dilatation and dissection, as well as their role as potential biomarkers, merit further validation. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2