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You are here: Contents > 2015 > Volume 24 Number 2 March 2015 > AORTIC VALVE DISEASE > The Effect of oxLDL on Aortic Valve Calcification via the Wnt/β-catenin Signaling Pathway: An Important Molecular Mechanism

The Effect of oxLDL on Aortic Valve Calcification via the Wnt/β-catenin Signaling Pathway: An Important Molecular Mechanism

Xu Gao1, Liwei Zhang2, Gangjian Gu3, Pin-Hui Wu4, Si Jin5, Weilin Hu2, Chengye Zhan2, Jun Li3, Yongsheng Li2

1Department of Pharmacy, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 3Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 4Tongji Medical College, Huazhong University of Science and Technology, First Clinical School of Medicine, 5Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background and aim of the study: Calcific aortic valve disease (CAVD) is a commonly acquired valvular disease. Although previous studies have shown valve calcification to be mediated by a chronic inflammatory disease process, with many similarities to atherosclerosis that included inflammatory cell infiltrates, lipoproteins, lipids, extracellular bone-matrix proteins, and bone minerals, little is known of the mechanisms of the cellular and molecular components and processes. It has recently been hypothesized that the calcific aortic valve is a product of active inflammation, similar to the atherosclerosis pathological process. Thus, the cessation of statin therapy should, in theory, have an effect on the treatment of CAVD and on aortic valve myofibroblasts (AVMFs), which play an important role in aortic valvular calcification. The study aim was to determine if oxidized low-density lipoprotein (oxLDL) could stimulate the apoptosis of AVMFs and the calcific-related pathway, and whether atorvastatin could inhibit the effects of AVMFs induced by oxLDL. The Wnt/GSK-3β/β-catenin signaling pathway may play a key role in this process, thereby making a major contribution to aortic valve calcification.

Methods: AVMFs were successfully acquired using a combination of trypsin and collagenase enzyme digestion, and made phenotypic for the identification for


alpha-smooth muscle actin (α-SMA). Cell apoptosis was monitored using flow cytometry, bone protein expression by Western blot, and related gene expression by reverse transcription polymerase chain reaction (RT-PCR).

Results: A positive identification of α-SMA, a myofibroblast marker, confirmed the successful harvesting of myofibroblasts. OxLDL significantly induced cell apoptosis (p <0.05), and this became even more obvious after 48 h (p <0.01). OxLDL also significantly increased the protein expression of all differentiation markers (p <0.05), as confirmed through Western blotting and RT-PCR, while atorvastatin significantly reduced the effects of oxLDL (p <0.05).

Conclusion: Among the mechanisms of the cellular and molecular components and processes, oxLDL increased the valve calcification-related signalling pathway by increasing extracellular bone-matrix protein that produces osteoblastic gene markers via the Wnt/GSK-3β/β-catenin pathway. And atorvastatin also prevented any oxLDL-induced effects through the same pathway, this may represent a new therapeutic target for CAVD, as an alternative to traditional valve replacement surgery.

The Journal of Heart Valve Disease 2015;24:190-196


The Effect of oxLDL on Aortic Valve Calcification via the Wnt/β-catenin Signaling Pathway: An Important Molecular Mechanism

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