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Oxidized HDL, as a Novel Biomarker for Calcific Aortic Valve Disease, Promotes the Calcification of Aortic Valve Interstitial Cells

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Abstract

Calcific aortic valve disease (CAVD) is characterized by progressive mineralization of the aortic valve. Lipid infiltration and oxidative stress are the driving forces for the initiation and development of this disease. However, it remains unknown whether oxidized high-density lipoprotein (ox-HDL) plays a role in the mineralization of aortic valve interstitial cells (AVICs). Serum ox-HDL levels were determined in 168 severe CAVD patients and 168 age- and gender-matched non-CAVD controls. Results showed that ox-HDL concentrations were significantly increased in CAVD compared with the control group (131.52 ± 30.96 ng/mL vs. 112.58 ± 32.20 ng/mL, P < 0.001) and were correlated with CAVD severity. Multivariable logistic regression revealed that ox-HDL levels were independently associated with CAVD after adjusting for the incidence of coronary artery disease (CAD) (odds ratio 1.019, 95% CI 1.012–1.027, P < 0.001) or atherosclerotic risk factors (odds ratio 1.027, 95% CI 1.017–1.037, P < 0.001). Chronic ox-HDL stimulation of AVICs increased alkaline phosphatase activity (ALP) and calcium deposits in AVICs in vitro. Mechanistic studies further showed that ox-HDL upregulated several osteogenic factors, including BMP-2, Runx2, and Msx2 expressions in AVICs. This is the first study to demonstrate a relationship between increased ox-HDL concentration and CAVD incidence.

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Funding

This work was supported by grants from the Chinese National Nature Science Foundation (81800223, 81470547 and 81500299), Shanghai Sailing Program (18YF1413500), and Joint Funds for the Innovation of Science and Technology, Fujian Province (2017Y9007).

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Author notes

  1. Jia Teng Sun, Yuan Yuan Chen and Jing Yan Mao contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Jia Teng Sun

  2. Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200025, People’s Republic of China

    Yuan Yuan Chen & Yan Liu

  3. Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, People’s Republic of China

    Yuan Yuan Chen, Jing Yan Mao, Yan Ping Wang, Ya Fen Chen & Ke Yang

  4. Department of Cardiac Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Xiang Hu

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  1. Jia Teng Sun
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All study protocols were approved by the Ethical Committee of Shanghai Jiao Tong University School of Medicine. Each participant provided written informed consent before the study commenced.

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Sun, J.T., Chen, Y.Y., Mao, J.Y. et al. Oxidized HDL, as a Novel Biomarker for Calcific Aortic Valve Disease, Promotes the Calcification of Aortic Valve Interstitial Cells. J. of Cardiovasc. Trans. Res. 12, 560–568 (2019). https://doi.org/10.1007/s12265-019-09903-3

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