Related Experiment Video

Updated: May 2, 2026

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

4.4K

Deletion of CXCR4 in cardiomyocytes exacerbates cardiac dysfunction following isoproterenol administration

E R Wang1, A A Jarrah1, L Benard1

  • 1Department of Medicine, Division of Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA.

Gene Therapy
|March 21, 2014
PubMed

Insights

Stromal cell-derived factor-1α (SDF-1α) and its receptor CXCR4 protect against heart failure by modulating beta-adrenergic signaling. This pathway prevents hypertrophy and improves cardiac function, offering a potential therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Adrenergic Signaling

Background:

  • Altered alpha- and beta-adrenergic receptor signaling contributes to cardiac hypertrophy and failure.
  • Stromal cell-derived factor-1α (SDF-1α)/CXCR4 axis is known for stem cell mobilization and cardioprotection post-injury.
  • The role of SDF-1/CXCR4 in acute protection against pathological hypertrophy and its mechanisms remain unclear.

Purpose of the Study:

  • To investigate whether SDF-1/CXCR4 signaling confers acute protection against pathological cardiac hypertrophy.
  • To elucidate the molecular mechanisms underlying SDF-1/CXCR4-mediated cardioprotection in the context of beta-adrenergic stimulation.
  • To determine the impact of CXCR4 on beta-adrenergic receptor-induced cardiac dysfunction.

Main Methods:

  • Utilized a mouse model with isoproterenol administration to induce cardiac hypertrophy.
  • Employing Cre-loxP-mediated gene recombination to selectively abrogate CXCR4 expression in cardiomyocytes.
  • Assessed cardiac function using fractional shortening and ejection fraction, and evaluated apoptosis and mitochondrial function.
  • Investigated the therapeutic potential of CXCR4 gene transfer using adeno-associated viral-9 vectors.

Main Results:

  • CXCR4 knockout mice exhibited exacerbated cardiac dysfunction, reduced fractional shortening and ejection fraction.
  • Ablation of CXCR4 increased susceptibility to isoproterenol-induced heart failure, marked by elevated apoptotic markers and impaired mitochondrial function.
  • CXCR4 gene transfer via AAV9 vectors improved mitochondrial function, reduced cardiac apoptosis, and restored cardiac function.
  • CXCR4 expression was found to prevent beta-adrenergic receptor-induced hypertrophy.

Conclusions:

  • SDF-1/CXCR4 signaling plays a critical role in mediating acute cardioprotection against pathological hypertrophy.
  • CXCR4 modulates beta-adrenergic receptor signaling, thereby preventing cardiac hypertrophy and dysfunction.
  • Targeting the SDF-1/CXCR4 pathway represents a promising therapeutic strategy for heart failure.

More Related Videos

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice05:08

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice

Published on: October 3, 2019

10.8K
Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

2.0K

Related Concept Videos

Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

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...
952
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

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...
645
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,...
790
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...
805
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...
4.8K