Layer-specific Nos3 expression and genotypic distribution in bicuspid aortic valve aortopathy.
Layer-specific Nos3 expression and genotypic distribution in bicuspid aortic valve aortopathy.
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二叶式主动脉瓣主动脉病中层特异性 Nos3 表达和基因型分布。
DOI：
10.1093/ejcts/ezac237
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Gleason,ThomasG
中科院分区：
文献类型：
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作者：
Hill,JenniferC;Billaud,Marie;Richards,TaraD;Kotlarczyk,MaryP;Shiva,Sruti;Phillippi,JulieA;Gleason,ThomasG
目的：我们推测二叶式主动脉瓣（BAV）主动脉病变中一氧化氮合酶3（Nos3）的表达和活性与组织层和Nos3基因型有关。方法检测升主动脉组织含内膜中层和外膜标本中Nos3和血小板和内皮细胞粘附分子1（Pecam1）的基因表达和NOS活性。确定非动脉瘤性 (NA) 和动脉瘤性 BAV 患者存在 2 个 Nos3 单核苷酸多态性（SNP；-786T/C 和 894G/T）（分别为 n=≥40、89）；患有三尖瓣主动脉瓣 (TAV) 和动脉瘤的患者 (n= 151)；结果：与 TAV 患者相比，在 BAV 患者的含内膜主动脉标本中观察到与 Pecam1 相关的 Nos3 升高和与管家基因相关的 Pecam1 降低。与 NA 主动脉标本相比，动脉瘤标本外膜中的 Nos3 较低，与瓣膜形态无关。相对于对照患者，各组中层/内膜的 NOS 活性相似，而患病外膜的 NOS 活性降低。动脉瘤 BAV 患者的 -786 SNP 野生型基因型代表性不足。 894 个 SNP 的基因型分布没有差异。与野生型细胞相比，-786 SNP 处至少有 1 C 等位基因的患者的原代内皮细胞表现出较低的 Nos3。结论这些中膜/内膜与外膜中 Nos3 的差异发现取决于瓣膜形态或动脉瘤，揭示了有关动脉瘤病理生理学的新信息，并支持我们持续的断言，即 BAV 和 TAV 患者中存在导致升主动脉病的不同机制。
OBJECTIVESWe hypothesized that expression and activity of nitric oxide synthase-3 enzyme (Nos3) in bicuspid aortic valve (BAV) aortopathy are related to tissue layer and Nos3 genotype.METHODSGene expression ofNos3andplatelet and endothelial cell adhesion molecule-1(Pecam1) and NOS activity were measured in intima-containing media and adventitial specimens of ascending aortic tissue. The presence of 2 Nos3 single-nucleotide polymorphisms (SNPs; −786T/C and 894G/T) was determined for non-aneurysmal (NA) and aneurysmal patients with BAV (n= 40, 89, respectively); patients with tricuspid aortic valve (TAV) and aneurysm (n= 151); and NA patients with TAV (n= 100).RESULTSElevatedNos3relative toPecam1and reducedPecam1relative to a housekeeping gene were observed within intima-containing aortic specimens from BAV patients when compared with TAV patients. LowerNos3in the adventitia of aneurysmal specimens was noted when compared with specimens of NA aorta, independent of valve morphology. NOS activity was similar among cohorts in media/intima and decreased in the diseased adventitia, relative to control patients. Aneurysmal BAV patients exhibited an under-representation of the wild-type genotype for −786 SNP. No differences in genotype distribution were noted for 894 SNP. Primary intimal endothelial cells from patients with at least 1 C allele at −786 SNP exhibited lowerNos3when compared with wild-type cells.CONCLUSIONSThese findings of differentialNos3in media/intima versus adventitia depending on valve morphology or aneurysm reveal new information regarding aneurysmal pathophysiology and support our ongoing assertion that there are distinct mechanisms giving rise to ascending aortopathy in BAV and TAV patients.