Related Experiment Video

Updated: Apr 1, 2026

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
10:21

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

10.8K

Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy

Alexander Grabner1, Ansel P Amaral2, Karla Schramm2

  • 1Katz Family Drug Discovery Center and Division of Nephrology and Hypertension, Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.

Cell Metabolism
|October 7, 2015
PubMed

Insights

Fibroblast growth factor 23 (FGF23) drives left ventricular hypertrophy (LVH) in chronic kidney disease (CKD) by activating fibroblast growth factor receptor 4 (FGFR4). Targeting FGFR4 may reduce cardiovascular risk in CKD patients.

Area of Science:

  • Cardiovascular research
  • Nephrology
  • Molecular biology

Background:

  • Chronic kidney disease (CKD) is a global health issue linked to cardiovascular complications like left ventricular hypertrophy (LVH).
  • Elevated fibroblast growth factor 23 (FGF23) levels in CKD are associated with LVH, but the underlying mechanism is unclear.
  • Identifying novel therapeutic targets is crucial for managing CKD-related cardiovascular risks.

Purpose of the Study:

  • To elucidate the specific fibroblast growth factor receptor (FGFR) mediating FGF23-induced LVH in CKD.
  • To investigate the signaling pathway activated by FGF23 in cardiac myocytes.
  • To evaluate FGFR4 as a potential pharmacological target for treating LVH in CKD.

Main Methods:

  • Investigated FGF23-FGFR interactions in cardiac myocytes.
  • Utilized cell signaling assays (phospholipase Cγ/calcineurin/nuclear factor of activated T cells).
  • Employed FGFR4-blocking antibodies in CKD rat models and genetically modified mice (FGFR4 knockout and gain-of-function).

Main Results:

  • FGF23 exclusively activates FGFR4 on cardiac myocytes.
  • FGFR4 activation stimulates the phospholipase Cγ/calcineurin/nuclear factor of activated T cells pathway.
  • FGFR4 blockade inhibited FGF23-induced cardiac myocyte hypertrophy and attenuated LVH in CKD rats.
  • FGFR4 deficiency prevented FGF23-induced LVH, while FGFR4 gain-of-function mutations caused spontaneous LVH.

Conclusions:

  • FGF23 promotes LVH in CKD by activating FGFR4 signaling in cardiac myocytes.
  • FGFR4 is a key mediator of cardiovascular complications in CKD.
  • Targeting FGFR4 represents a promising therapeutic strategy to mitigate cardiovascular risk in patients with CKD.

More Related Videos

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

7.8K
Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy08:34

Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy

Published on: September 25, 2017

25.8K

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...
1.4K
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...
718
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...
4.6K
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...
1.0K