Korean J Thorac Cardiovasc Surg.  2011 Dec;44(6):406-412. 10.5090/kjtcs.2011.44.6.406.

Adventitial Fibroblast Abormality in Thoracic Aortic Aneurysms and Aortic Dissections

• Suh JH
• Yoon JS
• Kim HW
• Jo KH

• KMID: 1447772
• DOI: http://doi.org/10.5090/kjtcs.2011.44.6.406

Abstract

BACKGROUND
Development of thoracic aortic aneurysms and aortic dissections (TAAD) is attributed to unbearable wall tension superimposed on defective aortic wall integrity and impaired aortic repair mechanisms. Central to this repair mechanisms are well-balanced and adequately functional cellular components of the aortic wall, including endothelial cells, smooth muscle cells (SMCs), inflammatory cells, and adventitial fibroblasts. Adventitial fibroblasts naturally produce aortic extracellular matrix (ECM), and, when aortic wall is injured, they can be transformed into SMCs, which in turn are involved in aortic remodeling. We postulated the hypothesis that adventitial fibroblasts in patients with TAAD may have defects in ECM production and SMC transformation.
MATERIALS AND METHODS
Adventitial fibroblasts were procured from the adventitial layer of fresh aortic tissues of patients with TAAD (Group I) and of multi-organ donors (Group II), and 4-passage cell culture was performed prior to the experiment. To assess ECM production, cells were treated with TNF-alpha (50 pM) and the expression of MMP-2 / MMP-3 was analyzed using western blot technique. To assess SMC transformation capacity, cells were treated with TGF-beta1 and expression of SM alpha-actin, SM-MHC, Ki-67 and SM calponin was evaluated using western blot technique. Fibroblasts were then treated with TGF-beta1 (10 pM) for up to 10 days with TGF-beta1 supplementation every 2 days, and the proportion of transformed SMC in the cell line was measured using immunofluorescence assay for fibroblast surface antigen every 2 days.
RESULTS
MMP-3 expression was significantly lower in group I than in group II. TGF-beta1-stimulated adventitial fibroblasts in group I expressed less SM alpha-actin, SM-MHC, and Ki-67 than in group II. SM-calponin expression was not different between the two groups. Presence of fibroblast was observed on immunofluorescence assay after more than 6 days of TGF-beta1 treatment in group I, while most fibroblasts were transformed to SMC within 4 days in group II.
CONCLUSION
ECM production and SMC transformation are compromised in adventitial fibroblasts from patients with TAAD. This result suggests that functional restoration of adventitial fibroblasts could well be a novel approach for the prevention and treatment of TAAD.

Keyword

Aorta; Aneurysm; Aortic dissection; Fibroblast

MeSH Terms

Actins
Aneurysm
Antigens, Surface
Aorta
Aortic Aneurysm, Thoracic
Azides
Blotting, Western
Calcium-Binding Proteins
Cell Culture Techniques
Cell Line
Deoxyglucose
Endothelial Cells
Extracellular Matrix
Fibroblasts
Fluorescent Antibody Technique
Humans
Microfilament Proteins
Myocytes, Smooth Muscle
Tissue Donors
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha
Actins
Antigens, Surface
Azides
Calcium-Binding Proteins
Deoxyglucose
Microfilament Proteins
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha