Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Pulmonary Hypertension: Classification and Pathogenesis

Pulmonary Hypertension: Classification and Pathogenesis

Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Spatial proteomics profiling reveals oncogene-specific immune niches and prognostic markers in NSCLC.

American journal of respiratory and critical care medicine·2026

Same author

IRG1/itaconate rewires macrophage and lung tumor metabolism through G6PD inhibition.

Cell metabolism·2026

Same author

Diagnostic yield and histopathological assessment of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy: a prospective comparison of two tunnelling approaches.

ERJ open research·2026

Same author

Spatial Protein Expression Analysis in Lungs Using Capillary-Based Immunoassay After Laser-Assisted Microdissection.

Cells·2026

Same author

Case Report: Tezepelumab as rescue therapy in near-fatal asthma requiring extracorporeal membrane oxygenation.

Frontiers in immunology·2026

Same author

Divergent CD45<sup>+</sup> immune landscapes shape the lung tumor microenvironment.

Frontiers in immunology·2026

Search research articles

Related Experiment Video

Updated: Dec 5, 2025

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Published on: May 13, 2019

IRAG1 Deficient Mice Develop PKG1β Dependent Pulmonary Hypertension.

Siladitta Biswas¹, Baktybek Kojonazarov^1,2, Stefan Hadzic¹

¹Universities of Giessen and Marburg Lung Centre, German Center for Lung Research (DZL), 35392 Giessen, Germany.

|October 17, 2020

Summary

Inositol trisphosphate receptor-associated cGMP-kinase substrate 1 (IRAG1) is crucial for pulmonary artery smooth muscle cell and right ventricular homeostasis. Its absence causes right ventricular dysfunction and pulmonary hypertension in mice.

Keywords:

IRAG1 PASMC PKG1β Pulmonary Hypertension RV dysfunction

More Related Videos

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

Published on: January 16, 2013

Isolation and Culture of Pulmonary Endothelial Cells from Neonatal Mice

Isolation and Culture of Pulmonary Endothelial Cells from Neonatal Mice

Published on: December 14, 2010

Related Experiment Videos

Last Updated: Dec 5, 2025

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Published on: May 13, 2019

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

Published on: January 16, 2013

Isolation and Culture of Pulmonary Endothelial Cells from Neonatal Mice

Isolation and Culture of Pulmonary Endothelial Cells from Neonatal Mice

Published on: December 14, 2010

Area of Science:

Cardiovascular Biology
Pulmonary Hypertension Pathophysiology
Molecular Signaling

Background:

cGMP-dependent protein kinase 1 (PKG1) has two isoforms, PKG1α and PKG1β.
Inositol trisphosphate receptor (IP3R)-associated cGMP-kinase substrate 1 (IRAG1) is a substrate of PKG1β and interacts with IP3RI, regulating intracellular calcium release.
The role of IRAG1 in pulmonary hypertension (PH) remains unknown.

Purpose of the Study:

To investigate the role of IRAG1 in the development of pulmonary hypertension and right ventricular (RV) function.
To elucidate the molecular mechanisms underlying IRAG1's function in pulmonary artery smooth muscle cells (PASMCs) and the RV.

Main Methods:

Wild-type (WT) and IRAG1 knockout (KO) mice were subjected to normoxic or hypoxic conditions for five weeks.
Echocardiography and right heart catheterization were performed to assess cardiac function and hemodynamics.
Lung and RV tissues were analyzed using immunostaining and western blotting; PASMCs were isolated for further study.

Main Results:

IRAG1 is expressed in PASMCs and downregulated under hypoxia.
IRAG1 deletion in mice resulted in RV hypertrophy, increased RV systolic pressure, and RV dysfunction.
Absence of IRAG1 impacted PKG1β expression in the lung and RV, leading to dysregulation of downstream targets.
IRAG1 KO mice spontaneously developed pulmonary hypertension.

Conclusions:

PKG1β signaling through IRAG1 is essential for maintaining PASMC and RV homeostasis.
Disruption of the IRAG1-PKG1β signaling complex contributes to RV dysfunction and the development of PH.
IRAG1 is a critical regulator in the pathogenesis of pulmonary hypertension.