Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve.

Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve.
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DOI:
10.1016/j.jtcvs.2013.04.028
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发表时间:
2014-03
影响因子:
6
通讯作者:
Gleason, Thomas G.
Gleason, Thomas G.
中科院分区:
医学1区
文献类型:
--
作者:
Phillippi, Julie A.;Green, Benjamin R.;Eskay, Michael A.;Kotlarczyk, Mary P.;Hill, Michael R.;Robertson, Anne M.;Watkins, Simon C.;Vorp, David A.;Gleason, Thomas G.

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患有二尖瓣主动脉瓣(BAV)的患者比患有退行性主动脉瓣(TAA)和患有三尖瓣主动脉瓣(TAV)的患者更容易在更早的年龄发生上升胸主动脉瘤(TAA)。经检验的假设是,bav相关的主动脉病变是由基质重塑机制介导的,这一机制与TAV患者的TAAs不同。在升主动脉置换术、主动脉瓣置换术和非动脉瘤供者和受者的心脏移植过程中采集主动脉标本。利用多光子显微镜对主动脉介质的基质结构进行定性评估,然后定量测定胶原蛋白和弹性蛋白纤维的取向。测定α-弹性蛋白含量,定量测定主动脉标本中未成熟和成熟胶原蛋白及赖氨酸氧化酶(Lox)的表达和活性,评价基质成熟度。测定主动脉平滑肌细胞基质金属蛋白酶(MMP)-2/9活性。相对于TAV-TAA患者,BAV-NA和BAV-TAA患者的弹性蛋白和胶原纤维排列更整齐,而TAV-TAA患者的弹性蛋白和胶原纤维排列比TAV-NA更混乱。α-弹性蛋白含量不变。与TAV-NA和TAV-TAA相比,BAV-NA和BAV-TAA中的未成熟胶原减少。成熟胶原中TAV-TAA含量高于TAV-NA和BAV-TAA。在TAV-TAA、BAV-NA和BAV-TAA标本中,Lox基因表达和活性以及MMP-2/9活性均有升高的趋势。BAV患者的高度排列的基质结构表明壁重塑不同于TAV-TAA。基质结构改变和胶原成熟度降低表明介导TAA重构的效应分子在BAV和TAV患者中是不同的。
Patients with bicuspid aortic valve (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 TAV patients. Aortic specimens were collected during ascending aortic replacement, aortic valve replacement and heart transplants from non-aneurysmal (NA) donors and recipients. Matrix architecture of the aortic media was assessed qualitatively using multi-photon 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 (MMP)-2/9 activity was quantified in aortic smooth muscle cells. Elastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA patients relative to TAV-TAA patients while TAV-TAA was more disorganized than TAV-NA. α-elastin content was unchanged. Immature collagen was reduced in BAV-NA and BAV-TAA when compared with TAV-NA and TAV-TAA. Mature collagen was elevated in TAV-TAA relative to TAV-NA and BAV-TAA. There was a trend toward elevated Lox gene expression and activity and MMP-2/9 activity for TAV-TAA, BAV-NA and BAV-TAA specimens. The highly aligned matrix architecture in BAV patients indicates that wall remodeling is distinct from TAV-TAA. Altered matrix architecture and reduced collagen maturity suggests that the effector molecules mediating remodeling of TAA are different in BAV and TAV patients.
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