Objective: To investigate the genetic contributions to the expression of cell surface adhesion molecules on endothelial cells (ECs) and to the release by ECs of chemokines, which are responsible for local inflammation. Methods and results: Monocyte adhesion to ECs and transmigration across the endothelial barrier are the key steps in the formation of atherosclerotic plaques and the rupture of the existing plaques. Biopsy specimens were obtained from the femoral arteries of 131 pedigreed baboons (65 males and 66 females) aged 10.4±1.5 years (mean±SD); arterial ECs were harvested and cultured up to the second passage and then subjected to in vitro challenge with tumor necrosis factor (TNF) α, 10 ng/mL, or vehicle for 4 hours. Endothelial surface adhesion molecules were measured using flow cytometry, and chemokines released by the ECs were measured by immunoassay. In response to TNF-α treatment, interleukin 8 and monocyte chemoattractant protein-1 released by ECs were increased 3.4-and 26-fold, respectively (P<0.001). The expressions of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were increased 12.2-, 41.4-, and 3.5-fold, respectively (P<0.001). The quantitative levels of several traits were heritable after TNF-α stimulation: h2=0.24 (P=0.02) for interleukin 8 and h 2=0.28 (P=0.003) for E-selectin in culture medium; h2=0.21 (P=0.03) for intercellular adhesion molecule-1; and h=0.37 (P<0.001) for vascular cell adhesion molecule-1 expression on EC surfaces. Furthermore, significant heritability was observed for lysate protein level, which is a measure of cell growth rate, with (h2=0.64, P<0.001) or without (h2=0.51, P<0.001) TNF-α stimulation. Conclusion: This study reports on the heritability of adhesion molecules in ECs when activated by TNF-α. This finding suggests genetic regulation of key arterial wall inflammatory processes that are responsible for the initiation of atherosclerotic lesions and the plaque rupture of existing atheromas.
|Idioma original||English (US)|
|Número de páginas||6|
|Publicación||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Estado||Published - ago. 2010|
|Publicado de forma externa||Sí|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine