Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Thorac Cardiovasc Surg. 2011 Oct;142(4):895-901. doi: 10.1016/j.jtcvs.2011.03.002. Epub 2011 Apr 9.
Patients with congenital bicuspid aortic valves have aortic valve stenosis at a relatively young age compared with patients with tricuspid aortic valves. We hypothesize that aortic valve stenosis evolves from a more aggressive inflammatory process, with increased macrophage/T-cell and neovessel content in congenital bicuspid aortic valveswhen compared with that seen in tricuspid valves.
Fifty-one severely stenotic aortic valves were obtained at the time of aortic valve replacement. A total of 17 bicuspid and 34 tricuspid aortic valves were evaluated. Macrophage/T-cell infiltration (CD68 plus CD3) and neovessel density (CD34) were evaluated with immunohistochemical staining. Leaflet calcification and ossification were also quantified. Real-time polymerase chain reaction was used to assess expression of chondromodulin 1 and vascular endothelial growth factor.
The density of macrophages/T cells was greater in congenital bicuspid aortic valves than in tricuspid valves (51 ± 31 vs 23 ± 13 cells/mm(2), P = .002). Neovascularization was more frequently noted in congenital bicuspid aortic valves when compared with tricuspid valves (31 ± 10 vs 21 ± 9 vessels/mm(2), P = .0005), and calcification was more severe (P = .03). Expression of chondromodulin 1 demonstrated a 6-fold downregulation (P = .0003) and expression of vascular endothelial growth factor demonstrated a 2-fold increase (P = .02) in congenital bicuspid aortic valves compared with that seen in tricuspid valves. Multivariable analyses demonstrated significant associations between bicuspid aortic valve anatomy and increased inflammatory cell infiltration (β = 25.8, P = .0007) and neovascularization (β = 9.4, P = .001), despite adjusting for measured covariates.
The pathogenesis of aortic valve stenosis in bicuspid aortic valves is associated with a more aggressive inflammatory process with increased macrophage infiltration and neovascularization when compared with that seen in tricuspid valves.
与三尖瓣主动脉瓣相比，先天性二叶主动脉瓣患者的主动脉瓣狭窄发生在相对年轻的年龄。我们假设主动脉瓣狭窄是由更具侵袭性的炎症过程引起的，与三尖瓣相比，先天性二叶主动脉瓣中巨噬细胞/T 细胞和新血管的含量增加。
在主动脉瓣置换时获得了 51 个严重狭窄的主动脉瓣。共评估了 17 个二叶瓣和 34 个三叶瓣。用免疫组织化学染色评估巨噬细胞/T 细胞浸润（CD68 加 CD3）和新血管密度（CD34）。还定量了瓣叶钙化和骨化。实时聚合酶链反应用于评估软骨调节素 1 和血管内皮生长因子的表达。
先天性二叶主动脉瓣中巨噬细胞/T 细胞的密度大于三尖瓣（51±31 与 23±13 个细胞/mm²，P=0.002）。与三尖瓣相比，先天性二叶主动脉瓣中更常观察到新生血管形成（31±10 与 21±9 个血管/mm²，P=0.0005），且钙化更严重（P=0.03）。与三尖瓣相比，先天性二叶主动脉瓣中软骨调节素 1 的表达下调了 6 倍（P=0.0003），血管内皮生长因子的表达增加了 2 倍（P=0.02）。多变量分析表明，尽管调整了测量的协变量，但二叶主动脉瓣解剖结构与炎症细胞浸润增加（β=25.8，P=0.0007）和新血管形成（β=9.4，P=0.001）之间存在显著关联。
与三尖瓣相比，二叶主动脉瓣主动脉瓣狭窄的发病机制与更具侵袭性的炎症过程相关，巨噬细胞浸润和新血管形成增加。
