Targeting CXCR1 and CXCR2 receptors in cardiovascular diseases
Kawthar Dhayni1, Kazem Zibara2, Hawra Issa3
1MP3CV Laboratory, UPJV UR 7517, Amiens, France.
Abstract:
CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), are expressed in a variety of cells including, leukocytes, fibroblasts, endothelial cells, and smooth muscle cells. Numerous intracellular mediators are activated by these G protein-coupled receptors based on several factors, including the nature of the ligand, its concentration, and the binding sites with the receptor, levels of the receptor, cell type, and stimulatory environment. Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily induce the chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease (CVD) progression. CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. These effects include reducing the atherosclerotic plaque area, improving the serum lipid profile, attenuation of the damage following ischemia-reperfusion, the regulation of blood pressure, and the restriction of cardiac remodeling. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great importance to limit the inflammatory complications associated with CVDs.
Insights
CXCR1 and CXCR2 inhibitors show promise for treating cardiovascular disease (CVD) by reducing inflammation and improving various health markers in animal models. Clinical trials are warranted to explore their therapeutic potential in human CVD patients.
Area of Science:
- Cardiovascular Science
- Immunology
- Pharmacology
Background:
- CXCR1 and CXCR2 (chemokine receptors) are activated by IL-8 and play a role in leukocyte chemotaxis during inflammation.
- Inflammation is a key process in the progression of cardiovascular disease (CVD).
Purpose of the Study:
- To investigate the therapeutic potential of CXCR1/2 inhibitors in cardiovascular disease models.
- To evaluate the impact of CXCR1/2 inhibition on inflammatory processes and CVD markers.
Main Methods:
- Review of studies on CXCR1/2 inhibitors in various animal models of CVD.
- Assessment of effects on atherosclerotic plaque area, lipid profiles, ischemia-reperfusion injury, blood pressure, and cardiac remodeling.
Main Results:
- CXCR1/2 inhibitors demonstrated beneficial effects across multiple CVD animal models.
- Observed improvements include reduced atherosclerotic plaque, better lipid profiles, attenuated ischemia-reperfusion damage, blood pressure regulation, and restricted cardiac remodeling.
Conclusions:
- CXCR1/2 inhibitors exhibit significant therapeutic potential for managing CVD by targeting inflammatory pathways.
- Further clinical investigation of CXCR1/2 inhibitors is crucial for their application in treating inflammatory complications of CVD.
More Related Videos
07:41A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
09:12Efficient Retroviral Transduction and Competitive Homing for Investigating GPCR-Mediated T-Cell Localization in Diverse Tissue Microenvironments
Published on: March 28, 2025
Related Concept Videos
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:30Coronary Artery Disease I: Introduction
01:15G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...