Grewal Nimrat, Gittenberger-de Groot Adriana C, Poelmann Robert E, Klautz Robert J M, Lindeman Johannes H N, Goumans Marie-José, Palmen Meindert, Mohamed Salah A, Sievers Hans-Hinrich, Bogers Ad J J C, DeRuiter Marco C
Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
J Thorac Cardiovasc Surg. 2014 Oct;148(4):1583-90. doi: 10.1016/j.jtcvs.2014.01.027. Epub 2014 Jan 25.
Patients with a bicuspid aortic valve have increased susceptibility to the development of ascending aortic dilation and dissection compared with persons with a tricuspid valve. To unravel a possible different mechanism underlying dilation in bicuspidy and tricuspidy, a comparison of the structure of the aortic wall was made.
Ascending aortic wall biopsies were divided into 4 groups: bicuspid (n=36) and tricuspid (n=23) without and with dilation. The expression of vascular smooth muscle cell maturation markers including lamin A/C, which plays a pivotal role in smooth muscle cell differentiation, and its splicing variant progerin indicative of aging, were studied immunohistochemically. Attention was also paid to the inflammatory status.
There is a significant difference in the structure and maturation of the aortic wall in bicuspidy, persisting in the dilated aortic wall, presenting with a thinner intima, lower expression of α smooth muscle actin, smooth muscle 22α, calponin, and almost absent expression of smoothelin. We show for the first time significantly lowered lamin A/C expression in bicuspidy. Progerin was found to be significantly increased in the media of the dilated wall in tricuspidy, also showing increased periaortic inflammation.
The structure of the nondilated and dilated aortic wall in bicuspidy and tricuspidy are intrinsically different, with the latter having more aspects of aging. In bicuspidy there is a defective smooth muscle cell differentiation possibly linked to lowered lamin A/C expression. Based on this vessel wall immaturity and increased susceptibility to dilation, different diagnostic and therapeutic approaches are warranted.
与三尖瓣患者相比，二叶式主动脉瓣患者升主动脉扩张和夹层形成的易感性增加。为了揭示二叶式和三叶式主动脉扩张背后可能存在的不同机制，对主动脉壁结构进行了比较。
升主动脉壁活检组织分为4组：未扩张的二叶式（n = 36）和三叶式（n = 23），以及扩张的二叶式和三叶式。免疫组化研究了血管平滑肌细胞成熟标志物的表达，包括在平滑肌细胞分化中起关键作用的核纤层蛋白A/C及其指示衰老的剪接变体早老蛋白。还关注了炎症状态。
二叶式主动脉壁的结构和成熟度存在显著差异，在扩张的主动脉壁中持续存在，表现为内膜较薄，α平滑肌肌动蛋白、平滑肌22α、钙调蛋白表达较低，平滑肌蛋白几乎不表达。我们首次发现二叶式中核纤层蛋白A/C表达显著降低。发现三叶式扩张壁中层中早老蛋白显著增加，主动脉周围炎症也增加。
二叶式和三叶式未扩张及扩张的主动脉壁结构本质上不同，后者具有更多衰老特征。在二叶式中，平滑肌细胞分化存在缺陷，可能与核纤层蛋白A/C表达降低有关。基于这种血管壁不成熟和扩张易感性增加，需要不同的诊断和治疗方法。
