A novel role of the sympatho-adrenergic system in regulating valve calcification

作者：Osman Lana; Chester Adrian H; Sarathchandra Padmini; Latif Najma; Meng Wenfang; Taylor Patricia M; Yacoub Magdi H^*

来源：Circulation, 2007, 116(11): I282-I287.

DOI：10.1161/CIRCULATIONAHA.106.681072

• valves
• calcification
• beta adrenergic receptors
• differentiation

Background - Aortic valve calcification is a progressive process resembling ossification. Recent evidence indicates that the sympathetic nervous system plays an important role in regulating bone deposition and resorption through the beta(2)-adrenergic receptors (beta(2)-ARs). The aim of this study is to determine the level and pattern of expression of beta 2-ARs in human valve interstitial cells (ICs) and assess their influence on differentiation of the cells into an osteoblast-like phenotype.
Methods and Results - Immunohistochemical analysis demonstrated a high expression of beta(2)-ARs, beta(1)-ARs, beta(3)-AR, s and receptor activator of nuclear factor-kappa B (RANK) in calcified aortic valves. The expression of beta(2-)ARs and beta(1)-ARs mRNA was assessed by real-time TaqMan PCR in cultures of human aortic valve ICs. Human valve ICs treated with the selective beta(2)-AR agonist, salmeterol, in the presence of osteogenic medium showed a significant 5-fold decrease in the alkaline phosphatase (ALP) activity in comparison to cells treated with osteogenic medium only (P < 0.05). Immunocytochemical staining of the valve ICs showed a concomitant reduction in osteocalcin expression. In addition, other beta(2)-AR agonists caused a reduction in the protein expression of bone markers including ALP, Cbfa-1, and periostin. Human valve ICs treated with norepinephrine, in the presence of osteogenic medium, did not show a significant reduction in the ALP activity.
Conclusions - These findings suggest an important role of the beta(2)-ARs in regulating valve calcification and may identify potential therapeutic targets.

• 出版日期2007-9-11
• 单位浙江大学