Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Thoracic Aortic Disease, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa.
Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
J Thorac Cardiovasc Surg. 2014 Mar;147(3):1056-64. doi: 10.1016/j.jtcvs.2013.04.028. Epub 2013 Jun 12.
Patients with bicuspid aortic valves (BAV) are predisposed to developing ascending thoracic aortic aneurysms (TAA) at an earlier age than patients who develop degenerative TAAs and have a tricuspid aortic valve (TAV). The hypothesis tested is that BAV-associated aortopathy is mediated by a mechanism of matrix remodeling that is distinct from that seen in TAAs of patients with tricuspid aortic valves.
Aortic specimens were collected during ascending aortic replacement, aortic valve replacement, and heart transplants from nonaneurysmal (NA) donors and recipients. Matrix architecture of the aortic media was assessed qualitatively using multiphoton microscopy followed by quantification of collagen and elastin fiber orientation. α-Elastin was determined and matrix maturity was assessed by quantifying immature and mature collagen and lysyl oxidase (Lox) expression and activity in aortic specimens. Matrix metalloproteinase-2/9 activity was quantified in aortic smooth muscle cells.
Elastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA cases than in TAV-TAA cases, whereas TAV-TAA cases were more disorganized than TAV-NA cases. α-Elastin content was unchanged. Immature collagen was reduced in BAV-NA and BAV-TAA cases when compared with TAV-NA and TAV-TAA cases. Mature collagen was elevated in TAV-TAA cases compared with TAV-NA and BAV-TAA cases. There was a trend toward elevated Lox gene expression and activity and matrix metalloproteinase-2/9 activity for TAV-TAA, BAV-NA, and BAV-TAA specimens.
The highly aligned matrix architecture in patients with BAVs indicates that wall remodeling is distinct from TAV-TAA. Altered matrix architecture and reduced collagen maturity suggest that the effector molecules mediating the remodeling of TAAs are different in BAV and TAV cases.
二叶式主动脉瓣（BAV）患者比三尖瓣主动脉瓣（TAV）患者更早发生退行性胸主动脉瘤（TAA），且更易发生升主动脉瘤。本研究旨在检验二叶式主动脉瓣相关主动脉病变是由不同于三尖瓣主动脉瓣 TAA 的基质重塑机制介导的假说。
本研究收集了升主动脉置换术、主动脉瓣置换术和心脏移植术中非动脉瘤（NA）供体和受者的升主动脉标本。采用多光子显微镜对主动脉中膜的基质结构进行定性评估，然后对胶原和弹性纤维的取向进行定量分析。通过定量检测主动脉标本中α-弹性蛋白、未成熟和成熟胶原以及赖氨酰氧化酶（Lox）的表达和活性，评估基质成熟度。定量分析主动脉平滑肌细胞中基质金属蛋白酶-2/9 的活性。
BAV-NA 和 BAV-TAA 病例的弹性纤维和胶原纤维比 TAV-TAA 病例排列更整齐，而 TAV-TAA 病例比 TAV-NA 病例更紊乱。α-弹性蛋白含量无变化。与 TAV-NA 和 TAV-TAA 病例相比，BAV-NA 和 BAV-TAA 病例的未成熟胶原减少。与 TAV-NA 和 BAV-TAA 病例相比，TAV-TAA 病例的成熟胶原升高。TAV-TAA、BAV-NA 和 BAV-TAA 标本的 Lox 基因表达和活性以及基质金属蛋白酶-2/9 活性呈升高趋势。
BAV 患者中高度排列的基质结构表明，壁重塑与 TAV-TAA 不同。基质结构的改变和胶原成熟度的降低表明，介导 TAA 重塑的效应分子在 BAV 和 TAV 病例中是不同的。
