Related Experiment Video

Updated: Dec 21, 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

4.4K

Cyclophilin A inhibition as potential treatment of human aortic valve calcification

Gianluca L Perrucci1, Paola Songia2, Donato Moschetta3

  • 1Unità di Medicina Rigenerativa e Biologia Vascolare, Centro Cardiologico Monzino IRCCS, Milano, Italy.

Pharmacological Research
|May 21, 2020
PubMed

Insights

Cyclophilin A (CyPA) drives aortic valve stenosis (AS) calcification by promoting calcium deposition in valve interstitial cells (VICs). Inhibiting CyPA may offer a new pharmacological treatment for AS.

Area of Science:

  • Cardiovascular Biology
  • Valvular Heart Disease Pathophysiology
  • Cellular Calcification Mechanisms

Background:

  • Aortic valve stenosis (AS) is the most common heart valve disease, affecting 3% of the population, characterized by calcification and impaired leaflet motility.
  • Valve interstitial cells (VICs) drive the calcification process in AS, but the precise molecular pathways remain incompletely understood.
  • Current pharmacological treatments for AS are limited, necessitating the identification of novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of Cyclophilin A (CyPA) in VIC-mediated calcification in the context of AS.
  • To determine if CyPA is upregulated in AS patient valves and if it influences VIC calcification in vitro.
  • To evaluate the potential of CyPA inhibition as a therapeutic strategy for AS.

Main Methods:

  • Analysis of CyPA expression in stenotic aortic valves from AS patients.
  • In vitro studies exposing VICs to pro-calcifying media to assess CyPA secretion.
  • Experimental treatment of VICs with exogenous CyPA and a Cyclosporine A (CsA) analogue (MM284) to evaluate effects on calcium deposition.

Main Results:

  • CyPA expression was found to be upregulated in stenotic AS valves.
  • Pro-calcifying conditions stimulated CyPA secretion by VICs.
  • Exogenous CyPA significantly enhanced calcium deposition in VICs.
  • Inhibition of exogenous CyPA using MM284 effectively reduced in vitro calcium deposition.

Conclusions:

  • CyPA plays a significant role in promoting VIC-mediated calcification, a key process in AS development.
  • CyPA is a potential therapeutic target for AS.
  • Inhibition of CyPA may represent a novel pharmacological approach for treating aortic valve stenosis.

Keywords:
Aortic valve stenosisCalcificationCyclophilin ACyclosporin A analoguePharmacological target

More Related Videos

Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat04:30

Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat

Published on: February 4, 2021

3.6K
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

3.1K

Related Concept Videos

Aortic Regurgitation III: Medical Management01:25

Aortic Regurgitation III: Medical Management

Aortic regurgitation (AR) is when the aortic valve does not close or seal properly, leading to backward blood circulation from the aorta into the left ventricle during diastole. Common causes of AR include rheumatic heart disease, congenital valve defects, and aortic root dilation. Managing AR requires a multifaceted approach to alleviate symptoms, preserve left ventricular function, and address the underlying cause of the regurgitation. Patients with symptomatic AR or significant left...
267
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
1.4K
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
259