Hinton Robert B, Juraszek Amy L, Opoka Amy M, Landis Benjamin J, Smith J Michael, Mecham Robert P, Bove Kevin E
Divisions of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Pediatric Cardiology, Wolfson Children's Hospital, Jacksonville, FL 32207, USA.
J Cardiovasc Dev Dis. 2021 Jun 25;8(7):75. doi: 10.3390/jcdd8070075.
Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.
弹性纤维断裂（EFF）是主动脉瓣疾病（AVD）的一个标志，并且新生血管形成已被确定为与炎症相关的晚期表现。我们试图描述早期EFF与异常血管生成之间的关系。为了研究疾病进展，我们使用组织化学、免疫组织化学和电子显微镜对早发型（<40岁）和晚发型（≥40岁）非综合征性AVD标本的主动脉瓣组织区域解剖结构和病理情况进行了评估。为了评估EFF对早期AVD进程的影响，我们还分析了威廉姆斯综合征和马凡综合征患者的瓣膜组织。二叶式主动脉瓣在早发型AVD中更为常见，而心血管合并症在晚发型AVD中更为常见。早发型AVD标本显示有血管生成，但无炎症或动脉粥样硬化。一种独特的弹性纤维成分模式围绕着早发型AVD新生血管，包括埃米林-1增加和纤连蛋白-5减少。威廉姆斯综合征（WS）和马凡综合征（MFS）的主动脉瓣存在不同类型的EFF；WS主动脉瓣有血管生成，而MFS主动脉瓣则没有。在无炎症的早发型AVD中发生异常血管生成，这与EFF有关。阐明潜在机制可能为新的药物治疗开发提供依据。
