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Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids

LI Yan-Qing¹, HUANG Pan-Na², ZHANG Hao-Zhe², HAN Lu-Yu², MIAO Ruo-Xiang², FENG Wan-Yun², PAN Hua³, FENG Lin⁴, WU Xin-Hua⁴, HE Juan⁴, TENG Xu^2,*, WANG Xiao-Ning⁴

¹Department of Gynaecology, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China；²Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China；³Medical Services Section, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China；⁴Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

Abstract

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Key words: chronic psychological stress; vascular calcification; glucocorticoids; endoplasmic reticulum stress

Received: 　　Accepted:

Corresponding author: 滕旭　　E-mail: tengxu78@hebmu.edu.cn

Citing This Article：

LI Yan-Qing, HUANG Pan-Na, ZHANG Hao-Zhe, HAN Lu-Yu, MIAO Ruo-Xiang, FENG Wan-Yun, PAN Hua, FENG Lin, WU Xin-Hua, HE Juan, TENG Xu, WANG Xiao-Ning. Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids. Acta Physiol Sin 2022; 74 (6): 927-938 (in Chinese with English abstract).