Wang Yongshi, Wu Boting, Dong Lili, Wang Chunsheng, Wang Xiaolin, Shu Xianhong
Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Heart Vessels. 2016 Feb;31(2):189-97. doi: 10.1007/s00380-014-0593-5. Epub 2014 Oct 18.
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.
二叶式主动脉瓣（BAV）在临床上有发展为主动脉病变的倾向，其中BAV产生的异常拉伸和剪切应力可诱导基质金属蛋白酶（MMPs）及其内源性组织抑制剂（TIMPs）的差异表达。与超声心动图显示主动脉瓣正常的BAV相比，狭窄性BAV在升主动脉处表现出额外的偏心高速血流喷射，进一步加剧了圆周收缩期壁切应力，它是否会导致独特的血浆MMP/TIMP模式仍不清楚。根据瓣膜病变和主动脉扩张状态，本研究纳入了93例BAV患者。A组（n = 37）和B组（n = 28）包括有或无升主动脉扩张的严重狭窄患者；C组（n = 12）和D组（n = 16）包括有或无升主动脉扩张的超声心动图正常的BAV患者。通过多重ELISA检测系统在单一程序中测定血浆MMP/TIMP水平（MMP-1、-2、-3、-8、-9、-10、-13和TIMP-1、-2、-4）。在孤立性严重主动脉狭窄患者中，当存在升主动脉扩张时，MMP-2和-9的血浆水平显著升高（分别为p = 0.001和p = 0.002）。然而，在升主动脉扩张的超声心动图正常的BAV患者中，MMP-2仍然是唯一升高的血浆成分（p = 0.027）。多变量分析显示，在孤立性严重狭窄的情况下，MMP-2和MMP-9均可作为主动脉扩张的独立危险因素（分别为p = 0.003和p = 0.001），在超声心动图正常的患者中MMP-2也是如此（p = 0.002）。总之，孤立性严重主动脉狭窄的BAV患者表现出独特的血浆MMP/TIMP模式，这可能被用作循环生物标志物以早期检测主动脉扩张。
