Kevin Windecker

Bicuspid aortic valve (BAV) is one of the most common types of congenital heart malformations1,2 and occurs in 0.5–2% of the population worldwide3. In this condition, the aortic valve, which typically is comprised of three leaflets, consists of only two1,2,3. BAV is associated with serious complications such as thoracic aortic aneurysm, aortic stenosis, aortic regurgitation, endocarditis, and general heart dysfunction. It has been discovered that levels of T and B lymphocytes including CD4 T Cells are lower in patients with BAV suggesting altered inflammatory responses compared to patients with normal tricuspid valves4. These findings give insight into thoracic aortic aneurysm formation. Aneurysmal lesions contain various cytokines and activation factors which suggest that TH1, TH2, TH17, and TH22 subsets are all present in aneurysmal lesions of BAV patients. Furthermore, since circulating level of these cells are not as high, it is proposed that these cells may be activated at the site of the lesion contributing to tissue degradation and other pathological characteristics of aortic aneurysm5.  CD4⁺AT2⁺ T lymphocytes are also present in high levels at the site of aneurysm and in circulation of thoracic aortic aneurysm patients6. This may attribute to the low progression of aortic aneurysm as these cells are known to play a role in growth inhibition, apoptosis inhibition and matrix metallopeptidases inhibition6. Further research should be focused on the role of CD4⁺AT2⁺ T lymphocytes and the role that the AT2 pathway plays in aortic aneurism. A better understanding of this mechanism may lead to better treatment of BAV related thoracic aortic aneurysm.

1. Shah SY, Higgins A, Desai MY. Bicuspid aortic valve: Basics and beyond. Cleve Clin J Med. 2018 Oct;85(10):779-784. doi: 10.3949/ccjm.85a.17069
2. van de Pol V, Kurakula K, DeRuiter MC, Goumans MJ. Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells? Front Physiol. 2017 Nov 30;8:938. doi: 10.3389/fphys.2017.00938
3. Liu T, Xie M, Lv Q, Li Y, Fang L, Zhang L, Deng W, Wang J. Bicuspid Aortic Valve: An Update in Morphology, Genetics, Biomarker, Complications, Imaging Diagnosis and Treatment. Front Physiol. 2019 Jan 30;9:1921. doi: 10.3389/fphys.2018.01921
4. Balistreri CR, Buffa S, Allegra A, et al. A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?. Oxid Med Cell Longev. 2018;2018:5879281. Published 2018 Apr 5. doi:10.1155/2018/5879281
5. Téo FH, de Oliveira RTD, Villarejos L, Mamoni RL, Altemani A, Menezes FH, Blotta MHSL. Characterization of CD4+ T Cell Subsets in Patients with Abdominal Aortic Aneurysms. Mediators Inflamm. 2018 Dec 27;2018:6967310. doi: 10.1155/2018/6967310
6. Wang C, Wu T, Hu X, Huang R, Lian F, Wang W, Feng Y, Xie B, Hu Z, Zhai X, Liu J, Gu J, Chen Y, Li J, Xue S. Identification and characterization of CD4(+)AT2(+) T lymphocyte population in human thoracic aortic aneurysm. Am J Transl Res. 2015 Feb 15;7(2):232-41.