Adventitial Fibroblast Abormality in Thoracic Aortic Aneurysms and Aortic Dissections
The Korean Journal of Thoracic and Cardiovascular Surgery
;
: 406-412, 2011.
Artículo
en Inglés
| WPRIM
| ID: wpr-19768
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 ANDMETHODS:
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Aorta
/
Azidas
/
Donantes de Tejidos
/
Proteínas de Unión al Calcio
/
Línea Celular
/
Western Blotting
/
Técnica del Anticuerpo Fluorescente
/
Actinas
/
Factor de Necrosis Tumoral alfa
/
Aneurisma de la Aorta Torácica
Límite:
Humanos
Idioma:
Inglés
Revista:
The Korean Journal of Thoracic and Cardiovascular Surgery
Año:
2011
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS