Related Experiment Video

Updated: May 13, 2026

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice
10:20

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

Published on: January 16, 2013

Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans

You-Yang Zhao1, Yidan D Zhao, Muhammad K Mirza

  • 1Department of Pharmacology and 2Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, USA. yyzhao@uic.edu

The Journal of Clinical Investigation
|June 3, 2009
PubMed

Insights

Loss of caveolin-1 causes pulmonary hypertension (PH) by increasing eNOS activity, impairing PKG. Targeting PKG nitration may offer a new therapeutic strategy for PH.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pathophysiology

Background:

  • Pulmonary hypertension (PH) is a severe condition characterized by increased pulmonary vascular resistance and right-sided heart failure.
  • Caveolin-1 (Cav1) plays a role in regulating endothelial nitric oxide synthase (eNOS) activity.

Purpose of the Study:

  • To investigate the role of caveolin-1 deficiency in the development of pulmonary hypertension.
  • To elucidate the molecular mechanisms linking eNOS activation, PKG impairment, and PH.
  • To explore potential therapeutic targets for PH.

Main Methods:

  • Utilized genetically modified mice with deletions in caveolin 1 (Cav1) and eNOS (Nos3).
  • Administered MnTMPyP (superoxide scavenger) and l-NAME (NOS inhibitor) to Cav1-/- mice.
  • Assessed pulmonary vascular remodeling and PH phenotype.
  • Investigated protein tyrosine nitration and protein kinase G (PKG) activity in lung tissue.
  • Analyzed human lung tissue from patients with idiopathic pulmonary arterial hypertension.

Main Results:

  • Loss of Cav1 in mice led to chronic eNOS activation, resulting in pulmonary vascular remodeling and PH.
  • Absence of eNOS (Nos3) in Cav1-/- mice prevented PH development, indicating eNOS's critical role.
  • Treatment with MnTMPyP or l-NAME reversed the PH phenotype in Cav1-/- mice.
  • eNOS activation in Cav1-/- lungs caused PKG impairment via tyrosine nitration.
  • Overexpression of PKG-1 rescued the PH phenotype in Cav1-/- mice.
  • Human idiopathic pulmonary arterial hypertension lung tissue showed increased eNOS activation, PKG nitration, and reduced Cav1.

Conclusions:

  • Loss of caveolin-1 induces pulmonary hypertension through hyperactive eNOS, leading to tyrosine nitration-dependent PKG impairment.
  • Targeting PKG nitration presents a promising novel therapeutic strategy for pulmonary hypertension.

More Related Videos

Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice08:02

Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice

Published on: October 20, 2013

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium08:46

Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium

Published on: September 1, 2015

Related Concept Videos

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 to...
Pulmonary Hypertension: Classification and Pathogenesis01:30

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...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
Chronic Obstructive Pulmonary Disease II: Emphysema01:23

Chronic Obstructive Pulmonary Disease II: Emphysema

Emphysema, a major phenotype of chronic obstructive pulmonary disease (COPD), is characterized by irreversible destruction of alveolar walls and permanent enlargement of distal airspaces. Unlike chronic bronchitis, which primarily affects the airways, emphysema predominantly involves the lung parenchyma, where structural damage leads to airflow limitation.PathophysiologyIt most commonly results from prolonged exposure to cigarette smoke and other toxic gases, particularly cigarette smoke.
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features01:24

Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features

Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...