Key result
Apelin attenuates human aortic valve interstitial cell calcification and osteoblastic differentiation via ERK and Akt pathways.
Why the study?
Although apelin has protective cardiovascular effects, its effects and mechanisms on the osteoblastic differentiation of aortic valve interstitial cells had not been elucidated.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for apelin in valvular calcification; leaves open clinical translation pending in vivo studies.
Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.
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Yuan et al. (2015) studied Aortic valve calcification (in vitro human aortic valve interstitial cells). Apelin vs. Pro-calcific medium alone (containing 10 mM beta-glycerophosphate disodium, 10 nM dexamethasone, and 50 μg/ml ascorbic acid) was evaluated on Osteoblastic differentiation and mineralization of human aortic valve interstitial cells (ALP activity/expression, Runx2 expression, and calcium content) (p=<0.05). Apelin (maximally at 100 pM) significantly attenuated ALP activity, Runx2 expression, and calcium content in human aortic valve interstitial cells via ERK and PI3-K/Akt pathways (p<0.05).
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