Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall Shear Stress Mapping.
Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall Shear Stress Mapping.
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DOI：
10.1016/j.jacc.2015.06.1310
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发表时间：
2015-08-25
影响因子：
24
通讯作者：
Fedak PW
中科院分区：
文献类型：
--
作者：
Guzzardi DG;Barker AJ;van Ooij P;Malaisrie SC;Puthumana JJ;Belke DD;Mewhort HE;Svystonyuk DA;Kang S;Verma S;Collins J;Carr J;Bonow RO;Markl M;Thomas JD;McCarthy PM;Fedak PW
二叶式主动脉瓣（BAV）患者升主动脉细胞外基质（ECM）失调的可疑遗传原因影响了BAV血管病手术切除的策略和阈值。使用四维（4D）心脏磁共振成像（CMR），我们已经证明了增加的局部壁剪切应力（WSS）在BAV患者的升主动脉。我们评估了WSS和BAV患者局部主动脉组织重塑之间的关系，以确定局部WSS对ECM表达失调的影响。接受升主动脉切除术的BAV患者（n = 20）接受术前4D Flow CMR以区域性标测WSS。配对主动脉壁样本（即，从升高和正常WSS区域获得的患者内样品），并通过组织学比较中膜弹性蛋白变性和通过蛋白质表达比较ECM调节。与WSS正常的相邻区域相比，WSS增加的区域显示出更大的内侧弹性蛋白降解：总弹性蛋白减少（p = 0.01），纤维更细（p = 0.00007），间隔更远（p = 0.001）。ECM调节分子的多重蛋白分析显示，在升高的WSS区域中，转化生长因子β-1（p = 0.04）、基质金属蛋白酶（MMP）-1（p = 0.03）、MMP-2（p = 0.06）、MMP-3（p = 0.02）和金属蛋白酶组织抑制剂-1（p = 0.04）增加，表明高WSS区域中ECM失调。WSS增加的区域与BAV患者升主动脉中ECM失调和弹性纤维变性相对应，表明瓣膜相关血流动力学是血管病发展的促成因素。需要进一步研究以验证4D Flow CMR作为疾病进展的非侵入性生物标志物的用途及其个性化切除策略的能力。
Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) has influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients. We assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation. BAV patients (n = 20) undergoing ascending aortic resection underwent preoperative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression. Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS. Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted.