Thorac Cardiovasc Surg 2019; 67(S 01): S1-S100
DOI: 10.1055/s-0039-1678971
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miR 29 and MMP-2 in the Proximal Aortic Aneurysm of BAV Patients: Worth a Try?

J. Haunschild
1   Saxonian Incubator for Clinical Translation, University of Leipzig, Leipzig, Germany
,
N. I. Schellinger
2   Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Leipzig, Germany
,
J. S. Barnard
1   Saxonian Incubator for Clinical Translation, University of Leipzig, Leipzig, Germany
,
K. von Aspern
3   University of Leipzig, Cardiac Surgery, Leipzig, Germany
,
F.-W. Mohr
3   University of Leipzig, Cardiac Surgery, Leipzig, Germany
,
D. C. Etz
3   University of Leipzig, Cardiac Surgery, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
28 January 2019 (online)

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Objectives: Patients with a bicuspid aortic valve (BAV) are prone to develop proximal aortic aneurysm. Matrix metalloproteinases (MMPs) play a major role in the destruction of extracellular matrix (ECM) in the aortic wall and have been largely discussed in aortic aneurysm development. However, this study correlates MMP-2 mRNA and protein quantity with enzyme activity in BAV and TAV patients as well as miRNA 29 A and B. The aim of the study is to gain a profound understanding of the role of MMP-2 and its regulation by miR 29 in the development of proximal aortic aneurysm in BAV patients.

Methods: Aortic samples from 111 patients (48 BAV, 29 TAV) were collected during cardiac surgery. MMP-2 mRNA, protein and activity levels were analyzed. The presence of SNPs for MMP-2 (rs2285052 and rs243865) was investigated using PCR.

Results: Patients with a BAV were significantly younger at time of surgery (p = 0.0029), had s significantly lower BMI, presented significantly more often with arterial hypertension (p = 0.005) and an additional valvular disease (p < 0.001) than patients with a TAV. A whole genome array of 16 patients was performed (8 BAV and 8 TAV patients). The results showed a significantly increased signal in BAV patients for MMP-2 (BAV: 9,251 ± 1,530 vs. 7,403 ± 1,334, p = 0.03) compared to TAV controls, while MMP-9, TIMP-1, and -2 displayed no significant differences between groups. Western Blot analysis revealed significant differences in the aortic protein expression of the aneurysmatic tissue between BAV and TAV patients with BAV patients showing twice as much MMP-2 protein (BAV: 1.12 ± 0.12 vs. TAV: 0.66 ± 0.06; p < 0.01). Data were confirmed by ELISA analysis. The higher protein level was also reflected by higher enzyme activity (BAV: 3.44 ± 0.21 vs. TAV: 2.90 ± 0.16; p = 0.04). As MMP-2 and -9 are described as targets of miR-29, a quantification was performed and showed a significant downregulation of miR29A in BAV patients (BAV: 0.79 ± 0.06 vs. TAV: 1.11 ± 0.08, p = 0.004). However, miR-29B1 and miR-29B2 showed no significant differences between the groups.

Conclusions: Patients with BAV have a higher mRNA and protein level resulting in an increased enzyme activity possibly regulated by miR29A.