Melatonin enhances atherosclerotic plaque stability by inducing prolyl-4-hydroxylase α1 expression.

Abstract:

OBJECTIVE:Melatonin, an endogenous neurohormone secreted predominately by the pineal gland, has a variety of physiological functions. However, its protective role in atherosclerosis is not clear. In this study, we sought to investigate the potential effects of melatonin in modulating atherosclerotic plaque stability in apolipoprotein E knockout (ApoE) mice. METHOD AND RESULTS:Smooth muscle cells were treated with melatonin, which significantly increased mRNA and protein levels of a key intracellular enzyme essential for collagen maturation and secretion, prolyl-4-hydroxylase α1 (P4Hα1). Mechanistically, melatonin increased Akt phosphorylation and transcriptional activation of specificity protein 1 (Sp1), which bound with the P4Hα1 promoter and then induced P4Hα1 expression. Pretreatment with either Akt inhibitor LY294002 or Sp1 inhibitor mithramycin A (MTM) could inhibit melatonin-induced P4Hα1 expression. Finally, atherosclerotic lesions were induced by placing a perivascular collar on the right common carotid artery of ApoE mice, which were received with or without different doses of melatonin or MTM. High-dose melatonin enhanced atherosclerotic plaque stability in ApoE mice in vivo by inducing the expression of P4Hα1, which was reversed by MTM. CONCLUSION:We propose that melatonin supplementation may provide a novel and promising approach to atherosclerosis treatment.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Li H,Li J,Jiang X,Liu S,Liu Y,Chen W,Yang J,Zhang C,Zhang W

doi

10.1097/HJH.0000000000001979

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

964-971

issue

5

eissn

0263-6352

issn

1473-5598

journal_volume

37

pub_type

杂志文章
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    更新日期:2018-08-01 00:00:00

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    更新日期:2016-12-01 00:00:00

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    pub_type: 杂志文章,多中心研究,随机对照试验

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    更新日期:2006-02-01 00:00:00

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    doi:

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