Related Experiment Video

Updated: Mar 21, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

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

Published on: May 31, 2016

20.6K

Bone Morphogenetic Protein Signaling Is Required for Aortic Valve Calcification

M Victoria Gomez-Stallons1, Elaine E Wirrig-Schwendeman1, Keira R Hassel1

  • 1From the Heart Institute, Cincinnati Children's Hospital Medical Center, OH (M.V.G.-S., E.E.W.-S., K.R.H., K.E.Y.); Department of Pediatrics, College of Medicine, University of Cincinnati, OH (M.V.G.-S., K.E.Y.); and Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN (S.J.C.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|May 21, 2016
PubMed

Insights

Bone morphogenetic protein (BMP) signaling drives calcific aortic valve disease (CAVD) by promoting osteochondrogenic gene induction in aortic valve interstitial cells. Inhibiting BMP signaling prevents aortic valve calcification, offering a potential therapeutic target for CAVD.

Area of Science:

  • Cardiovascular Biology
  • Bone Biology
  • Biomaterials Science

Background:

  • Calcific aortic valve disease (CAVD) is a prevalent heart valve condition characterized by calcific nodules leading to aortic valve stenosis.
  • The underlying mechanisms of CAVD remain largely unknown, though studies suggest a role for bone morphogenetic protein (BMP) signaling.
  • Klotho-deficient mice exhibit premature aging and develop aortic valve calcification, mirroring human CAVD.

Purpose of the Study:

  • To investigate the role of BMP signaling in the development of CAVD.
  • To examine BMP signaling activation and its correlation with calcification in Klotho-deficient mice and porcine aortic valve interstitial cells (VICs).

Main Methods:

  • Analysis of pSmad1/5/8 expression in Klotho(-/-) mice to assess BMP signaling activation.
  • In vitro studies using porcine VICs treated with osteogenic media.
  • Genetic inactivation of the BMP type IA receptor in Klotho(-/-) aortic VICs.
  • Inhibition of BMP pathway in osteogenic media-treated VICs.

Main Results:

  • BMP signaling activation (pSmad1/5/8 expression) precedes and co-localizes with aortic valve calcification in Klotho(-/-) mice.
  • Calcified Klotho(-/-) aortic valves show cellular and extracellular matrix changes resembling bone formation, with increased osteochondrogenic gene expression.
  • In vitro, osteogenic media induced BMP pathway activation, osteochondrogenic gene expression, and calcific nodule formation in porcine VICs.
  • Genetic inactivation or pharmacological inhibition of BMP signaling in VICs prevented aortic valve calcification.

Conclusions:

  • BMP signaling and osteochondrogenic gene induction are active in calcified aortic valves in both Klotho(-/-) mice and porcine VICs.
  • BMP signaling is essential for the development of aortic valve calcification in vitro and in vivo.
  • Targeting BMP signaling represents a potential therapeutic strategy for CAVD.
Abstract

Keywords:
BMPKlothoaortic valve calcificationheart valve diseaseosteogenesis

More Related Videos

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro05:47

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

Published on: May 10, 2021

4.8K
Isolation of Human Primary Valve Cells for In vitro Disease Modeling07:31

Isolation of Human Primary Valve Cells for In vitro Disease Modeling

Published on: April 16, 2021

3.3K

Related Concept Videos

Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
12.1K
Aortic Regurgitation I: Introduction01:15

Aortic Regurgitation I: Introduction

IntroductionAortic regurgitation is characterized by the backward flow of blood from the aorta into the left ventricle during diastole and arises from the improper closure of the aortic valve. This condition results in left ventricular volume overload and can stem from both acute and chronic etiologies, each contributing uniquely to the disease's progression and symptomatology.Acute and Chronic CausesAcute aortic regurgitation often results from events that suddenly impair the integrity of the...
1.1K
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
41.0K
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

8.1K
Aortic Regurgitation II: Clinical Features and Diagnostic Tests01:22

Aortic Regurgitation II: Clinical Features and Diagnostic Tests

Aortic valve regurgitation (AR) occurs when the aortic valve fails to close properly, allowing blood to flow backward from the aorta into the left ventricle. This backflow can result in two distinct clinical presentations: acute and chronic AR, each characterized by its own set of symptoms and physical findings.Acute Aortic RegurgitationAcute AR presents with a sudden onset of severe symptoms. Patients typically experience profound dyspnea (shortness of breath), chest pain, and signs of left...
826
Bone Formation by Intramembranous Ossification01:29

Bone Formation by Intramembranous Ossification

Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
13.9K