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Autonomous cortisol secretion promotes vascular calcification in vivo and in vitro under hyperaldosteronism

Hypertension Research volume 48, pages 366–377 (2025)Cite this article

A Comment to this article was published on 20 December 2024

Abstract

Autonomous cortisol secretion (ACS) is not uncommon in patients with primary aldosteronism (PA). However, the cardiovascular burden of ACS due to its dysregulated cortisol secretion remains poorly understood. Thus, we examined the effects of ACS on vascular calcification in a hyperaldosteronism environment in vitro and in vivo. A total of 339 patients with PA with adrenal incidentaloma and low-dose dexamethasone suppression test data (cutoff level: cortisol > 1.8 μg/dL) from a prospectively maintained database were enrolled; abdominal aortic calcification (AAC) scores were quantitatively estimated. Human aortic smooth muscle cells (HAOSMCs) were used as in vitro model of vascular calcification. In this study, 65 of the 339 patients with PA had ACS; 274 did not. Patients with PA/ACS had a higher AAC score (1171.0 ± 2434.0 vs. 489.5 ± 1085.3, P = 0.012) than patients without ACS. ACS was independently associated with AAC score (β = 0.139, P = 0.004) in multivariate analysis, and post-suppression cortisol level was significantly correlated with the AAC score (P = 0.004). In the HAOSMC model, co-treatment with cortisol synergistically stimulated alkaline phosphatase activity and calcium deposition in a hyperaldosteronism environment. The stimulatory effect of cortisol was abolished by the mineralocorticoid receptor (MR) antagonist eplerenone, but not glucocorticoid receptor antagonist mifepristone, indicating a MR-dependent mechanism. In conclusion, the presence of ACS is associated with heavier vascular calcification in patients with PA. Aldosterone and cortisol synergistically activate HAOSMC calcification via MR signaling, via a process that can be attenuated by eplerenone.

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Download references

The TAIPAI study group

Vin-Cent Wu12, Tai-Shuan Lai12, Shih-Chieh Jeff Chueh12, Shao-Yu Yang12, Kao-Lang Liu12, Chin-Chen Chang12, Bo-Ching Lee12, Shuo-Meng Wang12, Kuo-How Huang12, Po-Chih Lin12, Yen-Hung Lin12, Chi-Sheng Hung12, Lian-Yu Lin12, Shih-Cheng Liao12, Ching-Chu Lu12, Chieh-Kai Chan12, Leay-Kiaw Er13, Ya-Hui Hu13, Che-Hsiung Wu13, Yao-Chou Tsai13, Zheng-Wei Chen14, Chien-Ting Pan14, Che-Wei Liao15, Cheng-Hsuan Tsai12, Yi-Yao Chang16, Chen-Hsun Ho17, Wei-Chieh Huang18, Ying-Ying Chen19.

Funding

This study was supported by National Science and Technology Council (111-2314-B-002-250-MY2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Departments of Medical Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Bo-Ching Lee, Chin-Chen Chang, Victor Jing-Wei Kang & Jia-Zheng Huang

  2. Departments of National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Bo-Ching Lee, Yi-Yao Chang, Cheng-Hsuan Tsai & Zheng-Wei Chen

  3. Departments of Medical Imaging, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC

    Bo-Ching Lee

  4. Department of Business Administration and Graduate School of Service Management, Chihlee University of Technology, New Taipei City, Taiwan, ROC

    Yu-Li Lin & Yen-Hung Lin

  5. Departments of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Yi-Yao Chang, Cheng-Hsuan Tsai, Vin-Cent Wu, Chi-Sheng Hung & Yen-Hung Lin

  6. Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC

    Yi-Yao Chang

  7. Departments of Internal Medicine, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC

    Zheng-Wei Chen & Chien-Ting Pan

  8. Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan, ROC

    Che-Wei Liao

  9. Departments of Primary Aldosteronism Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Vin-Cent Wu & Yen-Hung Lin

  10. Departments of Cardiovascular Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Chi-Sheng Hung & Yen-Hung Lin

  11. Departments of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

    Chia-Hung Chou

  12. National Taiwan University Hospital, Taipei, Taiwan, ROC

    Vin-Cent Wu, Tai-Shuan Lai, Shih-Chieh Jeff Chueh, Shao-Yu Yang, Kao-Lang Liu, Chin-Chen Chang, Bo-Ching Lee, Shuo-Meng Wang, Kuo-How Huang, Po-Chih Lin, Yen-Hung Lin, Chi-Sheng Hung, Lian-Yu Lin, Shih-Cheng Liao, Ching-Chu Lu, Chieh-Kai Chan & Cheng-Hsuan Tsai

  13. Taipei Tzu-Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan, ROC

    Leay-Kiaw Er, Ya-Hui Hu, Che-Hsiung Wu & Yao-Chou Tsai

  14. Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan, ROC

    Zheng-Wei Chen & Chien-Ting Pan

  15. Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan, ROC

    Che-Wei Liao

  16. Department of Cardiovascular Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC

    Yi-Yao Chang

  17. Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC

    Chen-Hsun Ho

  18. Taipei Veterans General Hospital, Taipei, Taiwan, ROC

    Wei-Chieh Huang

  19. MacKay Memorial Hospital, Taipei, Taiwan, ROC

    Ying-Ying Chen

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  1. Bo-Ching Lee
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  2. Chin-Chen Chang
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  3. Victor Jing-Wei Kang
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  9. Che-Wei Liao
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  11. Vin-Cent Wu
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  12. Chi-Sheng Hung
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  13. Chia-Hung Chou
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  14. Yen-Hung Lin
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Consortia

On behalf of the TAIPAI study group

  • Vin-Cent Wu
  • , Tai-Shuan Lai
  • , Shih-Chieh Jeff Chueh
  • , Shao-Yu Yang
  • , Kao-Lang Liu
  • , Chin-Chen Chang
  • , Bo-Ching Lee
  • , Shuo-Meng Wang
  • , Kuo-How Huang
  • , Po-Chih Lin
  • , Yen-Hung Lin
  • , Chi-Sheng Hung
  • , Lian-Yu Lin
  • , Shih-Cheng Liao
  • , Ching-Chu Lu
  • , Chieh-Kai Chan
  • , Leay-Kiaw Er
  • , Ya-Hui Hu
  • , Che-Hsiung Wu
  • , Yao-Chou Tsai
  • , Zheng-Wei Chen
  • , Chien-Ting Pan
  • , Che-Wei Liao
  • , Cheng-Hsuan Tsai
  • , Yi-Yao Chang
  • , Chen-Hsun Ho
  • , Wei-Chieh Huang
  •  & Ying-Ying Chen

Contributions

Bo-Ching Lee project concept and design, data collection, imaging analysis, data analysis, and write-up. Victor Jing-Wei Kang data collection, imaging analysis, write-up. Chin-Chen Chang project concept and design. Jia-Zheng Huang data collection, imaging analysis. Yi-Yao Chang project concept and design. Cheng-Hsuan Tsai project concept and design. Zheng-Wei Chen project concept and design. Yu-Li Lin project concept and design. Chia-Hung Chou critical revisions. Che-Wei Liao critical revisions. Chien-Ting Pan critical revisions. Chi-Sheng Hung critical revisions. Vin-Cent Wu project concept and design, data collection, critical revisions. Yen-Hung Lin project concept and design, data collection, imaging analysis, critical revisions.

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Correspondence to Chia-Hung Chou or Yen-Hung Lin.

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Lee, BC., Chang, CC., Kang, V.JW. et al. Autonomous cortisol secretion promotes vascular calcification in vivo and in vitro under hyperaldosteronism. Hypertens Res 48, 366–377 (2025). https://doi.org/10.1038/s41440-024-01935-w

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