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Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis

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Abstract

Bicuspid aortic valve (BAV) exhibits a clinical incline toward aortopathy, in which aberrant tensile and shear stress generated by BAV can induce differential expression of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). Whether stenotic BAV, which exhibits additional eccentric high-velocity flow jet upon ascending aorta and further worsens circumferential systolic wall shear stress than BAV with echocardiographically normal aortic valve, can lead to unique plasma MMP/TIMP patterns is still unknown. According to their valvulopathy and aortic dilatation status, 93 BAV patients were included in the present study. Group A (n = 37) and B (n = 28) comprised severely stenotic patients with or without ascending aorta dilatation; Group C (n = 12) and D (n = 16) comprised echocardiographically normal BAV patients with or without ascending aorta dilatation. Plasma MMP/TIMP levels (MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4) were determined via a multiplex ELISA detection system in a single procedure. Among patients with isolated severe aortic stenosis, plasma levels of MMP-2 and -9 were significantly elevated when ascending aortic dilatation was present (p = 0.001 and p = 0.002, respectively). MMP-2, however, remained as the single elevated plasma component among echocardiographically normal BAV patients with dilated ascending aorta (p = 0.027). Multivariate analysis revealed that MMP-2 and MMP-9 could both serve as independent risk factor for aortic dilatation in the case of isolated severe stenosis (p = 0.003 and p = 0.001, respectively), and MMP-2 in echocardiographically normal patients (p = 0.002). In conclusion, BAV patients with isolated severe aortic stenosis demonstrated a distinct plasma MMP/TIMP pattern, which might be utilized as circulating biomarkers for early detection of aortic dilatation.

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Acknowledgments

The study was supported by the National Natural Science Foundation of China (Grant No. 81300232), the Shanghai Young Scientific ‘Phosphor’ Foundation (Grant No. 12QA1400700).

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Authors and Affiliations

  1. Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yongshi Wang, Lili Dong, Xiaolin Wang & Xianhong Shu

  2. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Yongshi Wang, Lili Dong, Chunsheng Wang & Xianhong Shu

  3. Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Boting Wu

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  1. Yongshi Wang
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  2. Boting Wu
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  3. Lili Dong
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  4. Chunsheng Wang
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  5. Xiaolin Wang
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  6. Xianhong Shu
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Correspondence to Xianhong Shu.

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Y. Wang and B. Wu contributed equally to this manuscript.

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Wang, Y., Wu, B., Dong, L. et al. Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis. Heart Vessels 31, 189–197 (2016). https://doi.org/10.1007/s00380-014-0593-5

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  • DOI: https://doi.org/10.1007/s00380-014-0593-5

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