Journal of Cardiovascular Translational Research

, Volume 12, Issue 6, pp 560–568 | Cite as

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

  • Jia Teng Sun
  • Yuan Yuan Chen
  • Jing Yan Mao
  • Yan Ping Wang
  • Ya Fen Chen
  • Xiang Hu
  • Ke YangEmail author
  • Yan LiuEmail author
Original Article


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.


Oxidized HDL Calcific aortic valve disease Aortic valve interstitial cells Calcification 


Funding Information

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).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

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.

Supplementary material

12265_2019_9903_MOESM1_ESM.docx (15 kb)
Supplementary Table 1 (DOCX 15 kb)
12265_2019_9903_MOESM2_ESM.docx (14 kb)
Supplementary Table 2 (DOCX 14 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jia Teng Sun
    • 1
  • Yuan Yuan Chen
    • 2
    • 3
  • Jing Yan Mao
    • 3
  • Yan Ping Wang
    • 3
  • Ya Fen Chen
    • 3
  • Xiang Hu
    • 4
  • Ke Yang
    • 3
    Email author
  • Yan Liu
    • 2
    Email author
  1. 1.Department of Cardiology, Ren Ji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Department of Cardiology, Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
  3. 3.Institute of Cardiovascular DiseaseShanghai Jiao Tong University School of MedicineShanghaiPeople’s Republic of China
  4. 4.Department of Cardiac SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

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