Related Experiment Video

Updated: Aug 28, 2025

Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents
07:26

Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents

Published on: July 14, 2021

5.2K

The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular

Shogo Ito1,2, Hisayuki Hashimoto1,3, Hiroyuki Yamakawa1,3

  • 1Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Nature Communications
|September 15, 2022
PubMed

Insights

The alternative complement pathway, specifically the C3-Cfd-C3aR axis, is crucial in right ventricular failure. Targeting this pathway offers potential new therapies for heart failure.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Molecular Medicine

Background:

  • Right ventricular failure is a critical component of heart failure with unclear mechanisms and limited specific therapies.
  • The alternative complement pathway, involving complement factor D (Cfd) and C3a receptor 1 (C3aR1), is implicated in cardiac function.

Purpose of the Study:

  • To investigate the role of the alternative complement pathway in right ventricular failure.
  • To identify potential therapeutic targets for right ventricular dysfunction.

Main Methods:

  • Gene expression analysis of right ventricular tissue.
  • Utilizing C3-knockout and Cfd-knockout mouse models of right ventricular failure.
  • Administering a C3a receptor antagonist in mouse models.
  • Correlating plasma Cfd levels with disease severity in human patients.

Main Results:

  • Right ventricles predominantly express alternative complement pathway genes (Cfd, C3aR1).
  • C3 and Cfd knockout attenuated right ventricular dysfunction and fibrosis in mice.
  • Plasma Cfd concentration correlated with right ventricular failure severity in patients.
  • C3a receptor antagonism significantly improved right ventricular function in mice.

Conclusions:

  • The C3-Cfd-C3aR axis plays a critical role in the pathogenesis of right ventricular failure.
  • This pathway represents a promising therapeutic target for treating right ventricular failure and associated heart conditions.

More Related Videos

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice09:40

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

Published on: May 13, 2019

10.6K
Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding10:39

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding

Published on: August 30, 2024

762

Related Concept Videos

Heart Failure II: Pathophysiology01:29

Heart 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...
31
Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
1.8K
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
489
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

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
Mitral Regurgitation I: Introduction01:20

Mitral Regurgitation I: Introduction

Mitral regurgitation is characterized by the backward circulation of blood from the left ventricle to the left atrium during systole, a phase of the cardiac cycle when the heart contracts and pumps blood out of the chambers. This abnormal flow occurs primarily due to the dysfunction of the mitral valve or its supporting structures, which include the mitral leaflets, chordae tendineae, annulus, and papillary muscles.Etiology and Mechanisms:Primary Mitral Regurgitation: This type arises from...
36
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy 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...
37