title: Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis.
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.
authors.affiliation: Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Yongshi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Boting
authors.initials: B
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Dong
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shu.xianhong@zs-hospital.sh.cn.|Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shu.xianhong@zs-hospital.sh.cn.
authors.forename: Xianhong
authors.initials: X
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D001014:Aortic Aneurysm / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D001021:Aortic Valve / Q000002:abnormalities*; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D001027:Aortography / Q000379:methods; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004108:Dilatation, Pathologic; D042241:Early Diagnosis; D015150:Echocardiography, Doppler; D005260:Female; D006349:Heart Valve Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D006801:Humans; D016014:Linear Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood
chemical_list: D015415:Biomarkers; D019714:Tissue Inhibitor of Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Aortic dilatation; Aortic stenosis; Bicuspid aortic valve; Matrix metalloproteinase