Ascending aorta dilation in association with bicuspid aortic valve: A maturation defect of the aortic wall

N Grewal, AC de Groot, RE Poelmann, RJM Klautz, JHN Lindeman, MJ Goumans, M (Meindert) Palmen, SA Mohamed, HH Sievers, Ad Bogers, MC DeRuiter

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)


Objective: 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. Methods: 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. Results: 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 a smooth muscle actin, smooth muscle 22a, 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. Conclusions: 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.
Original languageUndefined/Unknown
Pages (from-to)1583-1590
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number4
Publication statusPublished - 2014

Research programs

  • EMC COEUR-09

Cite this