Related Experiment Video
Updated: Aug 11, 2026
08:34
Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy
Published on: September 25, 2017
TNF alpha is required for hypoxia-mediated right ventricular hypertrophy
R M Smith1, J McCarthy, M N Sack
1Hatter Institute for Cardiology Research, University of Cape Town, Medical School, South Africa.
Molecular and Cellular Biochemistry
|May 17, 2001
Summary
Tumor necrosis factor-alpha (TNFα) plays a key role in chronic hypoxia-induced right ventricular hypertrophy. Mice lacking TNFα showed reduced pulmonary hypertension and cardiac remodeling during simulated high altitude.
Area of Science:
- Pulmonary Medicine
- Cardiovascular Physiology
- Immunology
Background:
- Hypoxia activates tumor necrosis factor-alpha (TNFα) in the lungs, inducing pulmonary vasoconstriction.
- The specific role of TNFα in chronic hypoxia-induced cardiopulmonary remodeling remains unclear.
Purpose of the Study:
- To investigate the role of TNFα in the development of right ventricular hypertrophy and pulmonary hypertension during chronic hypoxia.
- To evaluate the impact of TNFα deficiency on hypoxia-mediated cardiopulmonary responses.
Main Methods:
- Exposure of TNFα-null and wild-type mice to three weeks of hypobaric hypoxia (10% O2).
- Measurement of erythrocytosis, right ventricular systolic pressure, right ventricular hypertrophy, and lung wet weight.
Main Results:
- Both mouse strains developed similar erythrocytosis.
- Wild-type mice exhibited significant increases in right ventricular systolic pressure and hypertrophy, while TNFα-null mice did not.
- Lung wet weights increased similarly in both groups, suggesting TNFα's specific role in vascular and cardiac remodeling.
Conclusions:
- TNFα is integral to chronic hypoxia-induced right ventricular hypertrophy.
- TNFα signaling is a critical regulator of pulmonary hypertension and cardiac remodeling in response to sustained hypoxia.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:21Acute Respiratory Failure-II
Type I Respiratory Failure, or hypoxemic respiratory failure, occurs when the partial pressure of oxygen (PaO2) in arterial blood falls below 60 mmHg while breathing room air without a corresponding increase in arterial carbon dioxide levels (PaCO2). This condition highlights a significant impairment in the lungs' capacity to oxygenate the blood.
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
01:22Mitral Stenosis I: Introduction
Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
01:29Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
01:26Cellular Adaptation II: Hypertrophy
Hypertrophy is the increase in the size of individual cells, resulting in the enlargement of a tissue or organ. Unlike hyperplasia, which involves an increase in cell number, hypertrophy is characterized by an increase in cell volume. This process often occurs in response to higher functional demand or hormonal stimulation, leading to the production of more structural proteins and organelles, thereby enhancing the cells' work capacity.There are two primary types of hypertrophy: physiological...