Related Experiment Video
Updated: Mar 28, 2026
09:16
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
7.8K
CYLD-mediated DNA damage coordinates pathological cardiac hypertrophy via RIPK1-dependent signaling
Xianyun Jiang1, Mengyuan Shi1, Jiamin Guo1
1Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Journal of Molecular and Cellular Cardiology
|March 26, 2026
Summary
The deubiquitinating enzyme CYLD promotes heart failure by increasing DNA damage via RIPK1. Inhibiting CYLD or RIPK1 protects against cardiac remodeling and improves heart function.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Signaling
Background:
- Cardiac remodeling under pressure overload leads to heart failure.
- The deubiquitinating enzyme CYLD's role in this process is not fully understood.
Purpose of the Study:
- To investigate the role of CYLD in pressure overload-induced cardiac remodeling.
- To elucidate the molecular mechanisms by which CYLD affects cardiac hypertrophy and DNA damage.
Main Methods:
- Studied CYLD expression in hypertrophic mouse myocardium and cardiomyocytes.
- Utilized CYLD silencing and RIPK1 inhibition in experimental models.
- Assessed cardiac function, pathological remodeling, and DNA damage markers.
Main Results:
- CYLD expression was significantly upregulated in hypertrophic hearts.
- Silencing CYLD attenuated cardiac remodeling, improved function, and reduced DNA damage.
- CYLD deubiquitinates RIPK1, promoting apoptosis and DNA damage.
- RIPK1 inhibition synergized with CYLD silencing to reduce DNA damage.
Conclusions:
- The CYLD-RIPK1 axis is a critical regulator of DNA damage response in cardiac hypertrophy.
- CYLD inhibition is a potential therapeutic strategy for pressure overload-induced heart failure.
Related Concept Videos
01:23Rheumatic Heart Disease I: Introduction
849
Rheumatic heart disease or RHD is a chronic condition that results from rheumatic fever, causing permanent damage to the heart valves.Etiology and Risk FactorsIt primarily arises from rheumatic fever, an inflammatory disease that can develop after untreated or inadequately treated group A streptococcal (GAS) pharyngitis. Streptococcus spreads through direct contact with oral or respiratory secretions. While the bacteria are the causative agents, factors like malnutrition, overcrowding, poor...
849
01:21Myocarditis I: Introduction
568
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...
568
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
687
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...
687
01:30Cardiomyopathy II: Dilated Cardiomyopathy
746
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,...
746
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
798
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...
798
01:07MAPK Signaling Cascades
9.2K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.2K