Related Experiment Video
Updated: Aug 28, 2025
11:00
Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
10.2K
Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death
Nolan T Carew1,2, Heidi M Schmidt1,2, Shuai Yuan1
1Heart, Lung, Blood and Vascular Medicine Institute.
The Journal of Clinical Investigation
|September 15, 2022
Summary
Cytochrome b5 reductase 3 (CYB5R3) is vital for heart cell function. Its absence in male mice causes sudden cardiac death, linked to oxidative stress and genetic variants in Black individuals with heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Genetics
Background:
- Sudden cardiac death (SCD) in heart failure (HF) is linked to redox signaling imbalance in cardiomyocytes.
- The precise mechanisms of redox homeostasis in heart cells remain unclear.
Purpose of the Study:
- To investigate the role of cytochrome b5 reductase 3 (CYB5R3) in cardiomyocyte function and its connection to SCD.
- To identify potential genetic biomarkers for HF risk.
Main Methods:
- Generated a cardiomyocyte-specific CYB5R3-knockout mouse model (CYB5R3-KO).
- Analyzed cardiac function, electrophysiology, and molecular changes in KO mice.
- Examined the association of a CYB5R3 genetic variant (rs1800457) with event-free survival in patients with heart failure with reduced ejection fraction (HFrEF).
Main Results:
- CYB5R3 deletion in male adult cardiomyocytes caused cardiac hypertrophy, bradycardia, and SCD.
- CYB5R3-KO hearts exhibited calcium mishandling, ventricular fibrillation, reduced ATP, increased oxidative stress, and hemoprotein dysregulation.
- The CYB5R3 T117S variant correlated with ~20% decreased event-free survival in Black individuals with HFrEF.
Conclusions:
- CYB5R3 is essential for maintaining cardiomyocyte redox balance and function.
- CYB5R3 deficiency contributes to SCD through cardiac dysfunction and oxidative stress.
- The CYB5R3 T117S variant may serve as a genetic risk marker for HFrEF in individuals of African ancestry.
More Related Videos
09:36Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
1.3K
14:39Isolation and Functional Characterization of Human Ventricular Cardiomyocytes from Fresh Surgical Samples
Published on: April 21, 2014
17.5K
Related Concept Videos
01:25Cardiomyopathy I: Introduction and Classification
41
Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
41
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
37
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...
37
01:21Myocarditis I: Introduction
23
Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
23
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
21
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
21
01:28Mechanism of Cardiac Arrhythmias
1.0K
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
1.0K
01:30Cardiomyopathy II: Dilated Cardiomyopathy
19
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
19