Why the study?
The cellular and molecular mechanisms underlying calcific aortic valve stenosis and the potential pharmacological modulation of valve interstitial cell osteoblastic differentiation are not fully understood.
Does atorvastatin prevent osteoblast differentiation in human aortic valve interstitial cells?
Does atorvastatin prevent osteoblast differentiation in human aortic valve interstitial cells?
Atorvastatin reduces osteoblastic differentiation of human aortic valve interstitial cells in vitro, suggesting a potential mechanism for statins in preventing calcific aortic valve stenosis.
Answers are grounded in this paper and cite their sources.
In vitro atorvastatin effect on valve interstitial cells leaves open any clinical role in preventing calcific aortic stenosis.
BACKGROUND: Calcific aortic valve stenosis is a common disease in the elderly and is characterized by progressive calcification and fibrous thickening of the valve, but the cellular and molecular mechanisms are not fully understood. We hypothesized that human valve interstitial cells (ICs) are able to differentiate into osteoblast-like cells through the influence of defined mediators and that this process can be modulated pharmacologically. METHODS AND RESULTS: To test this hypothesis, we treated primary cultures of human aortic valve ICs with osteogenic media, bone morphogenic proteins ([BMPs] BMP-2, BMP-4, and BMP-7), and tissue growth factor-beta ([TGF-beta] TGF-beta1 and TGF-beta3) for 21 days. These mediators induced osteoblast differentiation of valve ICs by significantly increasing the activity and expression of alkaline phosphatase ([ALP] P<0.001). A cytokine protein array revealed that atorvastatin treatment (100 micromol/L) of human valve ICs caused a downregulation in levels of expression of BMP-2, BMP-6, TGF-beta1, and TGF-beta3 after 24 hours. In addition, human valve ICs treated with atorvastatin in the presence of osteogenic media showed a significant reduction in ALP activity in comparison to cells treated with osteogenic media only (P=<0.001). This was further confirmed with immunocytochemical staining of valve ICs, whereby atorvastatin markedly reduced the expression of ALP and osteocalcin induced by osteogenic media in comparison to untreated cells. CONCLUSIONS: These findings suggest that human valve ICs are capable of osteoblastic differentiation, by potential mediators which can be pharmacologically targeted by atorvastatin.
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Osman et al. (2006) studied this question.
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