Related Experiment Video

Updated: Sep 5, 2025

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro
05:47

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro

Published on: May 10, 2021

4.1K

Melatonin Inhibits NF-κB/CREB/Runx2 Signaling and Alleviates Aortic Valve Calcification

Shao-Jung Li1,2,3,4, Wan-Li Cheng2,3,4, Yu-Hsun Kao3,4,5,6

  • 1Division of Cardiovascular Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Frontiers in Cardiovascular Medicine
|July 7, 2022
PubMed

Insights

Melatonin, a hormone, reduces calcification in heart valve cells by inhibiting key proteins. Targeting the melatonin MT1 receptor shows promise for treating calcific aortic valve disease (CAVD).

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Endocrinology

Background:

  • Calcific aortic valve disease (CAVD) is a significant cause of mortality.
  • Melatonin is known to inhibit pathways like nuclear factor-kappa B (NF-κB) and cyclic AMP response element-binding protein (CREB), which are implicated in CAVD progression.

Purpose of the Study:

  • To investigate the role of melatonin signaling, specifically through MT1 and MT2 receptors, in the calcification of valvular interstitial cells (VICs).
  • To elucidate the molecular mechanisms by which melatonin affects VIC calcification, focusing on the NF-κB/CREB/runt-related transcription factor 2 (Runx2) pathway.

Main Methods:

  • Porcine VICs were cultured in osteogenic medium with or without melatonin.
  • Western blotting and Alizarin red staining were employed to assess protein expression and calcification levels.
  • Chromatin immunoprecipitation (ChIP) assays were performed to analyze NF-κB binding to the Runx2 promoter.

Main Results:

  • Osteogenic medium significantly increased the expression of NF-κB, CREB, and Runx2, and promoted VIC calcification.
  • Melatonin treatment downregulated these osteogenic markers and reduced VIC calcification.
  • The anticalcification effect of melatonin was dependent on MT1 receptor activation, as indicated by blockade with Luzindole and an MT1-specific antibody, but not an MT2 inhibitor.
  • Melatonin attenuated NF-κB binding to the Runx2 promoter.

Conclusions:

  • Melatonin, via the MT1 receptor, inhibits VIC calcification by suppressing the NF-κB/CREB/Runx2 signaling pathway.
  • Targeting the melatonin/MT1 axis presents a potential therapeutic strategy for managing calcific aortic valve disease.
Keywords:
NF-κBcalcific aortic valve diseasecyclic AMP response element-binding proteinmelatoninosteogenesisrunt-related transcription factor 2valvular interstitial cell

More Related Videos

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

19.7K
Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification08:55

Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification

Published on: November 20, 2017

9.9K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.8K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.5K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.2K