Progressive Development of Aberrant Smooth Muscle Cell Phenotype in Abdominal Aortic Aneurysm Disease.
J Vasc Res
; 55(1): 35-46, 2018.
Article
en En
| MEDLINE
| ID: mdl-29232676
ABSTRACT
Abdominal aortic aneurysm (AAA) is a silent, progressive disease with a high mortality and an increasing prevalence with aging. Smooth muscle cell (SMC) dysfunction contributes to gradual dilatation and eventual rupture of the aorta. Here we studied phenotypic characteristics in SMC cultured from end-stage human AAA (≥5 cm) and cells cultured from a porcine carotid artery (PCA) model of early and end-stage aneurysm. Human AAA-SMC presented a secretory phenotype and expressed elevated levels of the differentiation marker miR-145 (2.2-fold, p < 0.001) and the senescence marker SIRT-1 (1.3-fold, p < 0.05), features not recapitulated in aneurysmal PCA-SMC. Human and end-stage porcine aneurysmal cells were frequently multi-nucleated (3.9-fold, p < 0.001, and 1.8-fold, p < 0.01, respectively, vs. control cells) and displayed an aberrant nuclear morphology. Human AAA-SMC exhibited higher levels of the DNA damage marker γH2AX (3.9-fold, p < 0.01, vs. control SMC). These features did not correlate with patients' chronological age and are therefore potential markers for pathological premature vascular aging. Early-stage PCA-SMC (control and aneurysmal) were indistinguishable from one another across all parameters. The principal limitation of human studies is tissue availability only at the end stage of the disease. Refinement of a porcine bioreactor model would facilitate the study of temporal modulation of SMC behaviour during aneurysm development and potentially identify therapeutic targets to limit AAA progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Rotura de la Aorta
/
Aneurisma de la Aorta Abdominal
/
Miocitos del Músculo Liso
/
Músculo Liso
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Vasc Res
Asunto de la revista:
ANGIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido