Related Experiment Video

Updated: Jul 21, 2025

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption
09:20

Perturbing Endothelial Biomechanics via Connexin 43 Structural Disruption

Published on: October 4, 2019

5.6K

Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease

Shu Xian Loh1, Yasemin Ekinci2, Luke Spray2

  • 1Department of Cardiology, Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.

Journal of Clinical Medicine
|July 29, 2023
PubMed

Insights

Targeting the fractalkine receptor CX3CR1 may reduce heart failure after myocardial infarction (MI). Inhibiting CX3CR1 in a rat model decreased infarct size and inflammation, suggesting a new therapeutic avenue for heart attack patients.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Pharmacology

Background:

  • Acute myocardial infarction (MI) can lead to heart failure (HF) due to impaired healing and adverse left ventricular remodeling.
  • Ischaemia/reperfusion injury (IRI), characterized by intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO), contributes to HF post-MI.
  • Current pharmacological strategies targeting IRI or HF post-MI have shown limited success, and anti-inflammatory therapies risk immune system effects.

Purpose of the Study:

  • To review the cellular biology of fractalkine (FKN, CX3CL1) and its receptor CX3CR1.
  • To explore the potential of targeting CX3CR1 as a therapeutic strategy for myocardial infarction (MI) and subsequent heart failure (HF).
  • To present ongoing studies investigating CX3CR1 inhibition for coronary artery disease.

Main Methods:

  • Review of existing literature on fractalkine/CX3CR1 biology and its role in cardiovascular disease.
  • Analysis of preclinical data from a rat MI model using a CX3CR1 antagonist (KAND567).
  • Examination of clinical data associating CX3CR1 with microvascular obstruction (MVO) in patients undergoing primary percutaneous coronary intervention (PCI).

Main Results:

  • Fractalkine receptor CX3CR1 is linked to microvascular obstruction (MVO) in patients post-MI.
  • Inhibition of CX3CR1 in a rat MI model significantly reduced infarct size, inflammation, intramyocardial hemorrhage (IMH), and microvascular obstruction (MVO).
  • The fractalkine/CX3CR1 axis plays a role in the pathophysiology of MI and subsequent cardiac remodeling.

Conclusions:

  • CX3CR1 antagonism presents a promising therapeutic target to mitigate IRI and prevent adverse remodeling post-MI.
  • Targeting CX3CR1 may offer a novel approach to reduce infarct size and prevent heart failure development after acute myocardial infarction.
  • Further investigation into CX3CR1 inhibition is warranted for patients with coronary artery disease and myocardial infarction.

Keywords:
CX3CR1FRACTAL trialT lymphocytesacute myocardial infarctionatherosclerosisfractalkineinflammationmonocytes

More Related Videos

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty10:03

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty

Published on: January 28, 2020

5.3K
A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 406:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

13.8K

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.7K
Coronary Artery Disease II: Pathophysiology01:26

Coronary Artery Disease II: Pathophysiology

Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
12
Acute Coronary Syndrome II: Pathophysiology and Clinical Manifestations01:19

Acute Coronary Syndrome II: Pathophysiology and Clinical Manifestations

The pathophysiology of Acute Coronary Syndrome [ACD] involves several key processes:The main underlying cause of ACD is atherosclerosis, a chronic inflammatory disease characterized by the buildup of lipid-laden plaques within the coronary arteries.As the atherosclerotic plaque grows in the coronary artery, it may become unstable due to the formation of a lipid-rich core and a thin fibrous cap. Inflammatory cells within the plaque, such as macrophages, secrete enzymes that degrade the...
20
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
20
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K