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

Bo-Ching Lee^{1

2

3}, Chin-Chen Chang¹, Victor Jing-Wei Kang¹, Jia-Zheng Huang¹, Yu-Li Lin⁴, Yi-Yao Chang^{2

5

6}, Cheng-Hsuan Tsai^{2

5}, Zheng-Wei Chen^{2

7}, Che-Wei Liao⁸, Chien-Ting Pan⁷, Vin-Cent Wu^{5

9}, Chi-Sheng Hung^{5

10}, Chia-Hung Chou¹¹, Yen-Hung Lin^{12

13

14

15}; TAIPAI study group

Collaborators, Affiliations

Collaborators

Affiliations

¹ Departments of Medical Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
² Departments of National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
³ Departments of Medical Imaging, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC.
⁴ Department of Business Administration and Graduate School of Service Management, Chihlee University of Technology, New Taipei City, Taiwan, ROC.
⁵ Departments of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
⁶ Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC.
⁷ Departments of Internal Medicine, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC.
⁸ Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan, ROC.
⁹ Departments of Primary Aldosteronism Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹⁰ Departments of Cardiovascular Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹¹ Departments of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. joan640124@yahoo.com.tw.
¹² Department of Business Administration and Graduate School of Service Management, Chihlee University of Technology, New Taipei City, Taiwan, ROC. austinr34@gmail.com.
¹³ Departments of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.
¹⁴ Departments of Primary Aldosteronism Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.
¹⁵ Departments of Cardiovascular Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.

PMID: 39516366
DOI: 10.1038/s41440-024-01935-w

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

Bo-Ching Lee et al. Hypertens Res. 2025 Jan.

. 2025 Jan;48(1):366-377.

doi: 10.1038/s41440-024-01935-w. Epub 2024 Nov 8.

Authors

Collaborators

Affiliations

¹ Departments of Medical Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
² Departments of National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
³ Departments of Medical Imaging, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC.
⁴ Department of Business Administration and Graduate School of Service Management, Chihlee University of Technology, New Taipei City, Taiwan, ROC.
⁵ Departments of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
⁶ Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan, ROC.
⁷ Departments of Internal Medicine, National Taiwan University Hospital Yun-lin Branch, Douliu, Taiwan, ROC.
⁸ Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan, ROC.
⁹ Departments of Primary Aldosteronism Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹⁰ Departments of Cardiovascular Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
¹¹ Departments of Obstetrics and Gynecology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. joan640124@yahoo.com.tw.
¹² Department of Business Administration and Graduate School of Service Management, Chihlee University of Technology, New Taipei City, Taiwan, ROC. austinr34@gmail.com.
¹³ Departments of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.
¹⁴ Departments of Primary Aldosteronism Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.
¹⁵ Departments of Cardiovascular Center, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. austinr34@gmail.com.

PMID: 39516366
DOI: 10.1038/s41440-024-01935-w

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.

Keywords: Abdominal*; Aorta; Cardiovascular Diseases/etiology*; Humans; Hypertension; Primary aldosteronism.

PubMed Disclaimer

Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests.

Comment in

Synergistic interplay between cortisol and aldosterone: unveiling mechanisms of vascular calcification in hyperaldosteronism.
Wang CY, Ou HY. Wang CY, et al. Hypertens Res. 2025 Mar;48(3):1231-1233. doi: 10.1038/s41440-024-02071-1. Epub 2024 Dec 20. Hypertens Res. 2025. PMID: 39706886

References

1. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48:2293–300. - PubMed
1. Hiraishi K, Yoshimoto T, Tsuchiya K, Minami I, Doi M, Izumiyama H, et al. Clinicopathological features of primary aldosteronism associated with subclinical Cushing’s syndrome. Endocr J. 2011;58:543–51. - PubMed
1. Tang L, Li X, Wang B, Ma X, Li H, Gao Y, et al. Clinical characteristics of aldosterone- and cortisol-coproducing adrenal adenoma in primary aldosteronism. Int J Endocrinol. 2018;2018:4920841. - PubMed - PMC
1. Piaditis GP, Kaltsas GA, Androulakis II, Gouli A, Makras P, Papadogias D, et al. High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas. Clin Endocrinol. 2009;71:772–8.
1. Peng KY, Liao HW, Chan CK, Lin WC, Yang SY, Tsai YC, et al. Presence of subclinical hypercortisolism in clinical aldosterone-producing adenomas predicts lower clinical success. Hypertension. 2020;76:1537–44. - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Supplementary concepts

Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Comment in

References

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources