Journal Article

CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon transverse aortic constriction

Kleiner, Jan Lukas, Duerr, Georg Daniel, Niepmann, Sven Thomas, Eichhorn, Lars, Coburn, Mark, Frede, Stilla, Rodrigo, Maria Belen, Weisheit, Christina Katharina, Zimmer, Sebastian, Kurts, Christian

2021

Overview

The CX3CL1/CX3CR1 axis mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and plays a pivotal role in the inflammation-driven pathology of cardiovascular disease. The cardiac immune response differs depending on the underlying causes. This suggests that for the development of successful immunomodulatory therapy in heart failure due to chronic pressure overload induced left ventricular (LV) hypertrophy, the underlying immune patterns must be examined. Here, the authors demonstrate that Fraktalkine-receptor CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in a mouse model of transverse aortic constriction (TAC). The comparison of C57BL/6 mice with CX3CR1 deficient mice displayed reduced LV hypertrophy and preserved cardiac function in response to pressure overload in mice lacking CX3CR1. Moreover, the normal immune response following TAC induced pressure overload which is dominated by Ly6C low macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6C high macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6C high monocytes infiltrated the heart in response to a C-C chemokine ligand 2 burst. CX3CR1 expression impacts the immune response in the development of LV hypertrophy and its absence has clear cardioprotective effects. Hence, suppression of CX3CR1 may be an important immunomodulatory therapeutic target to ameliorate pressure-overload induced heart failure.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abbreviations / Anesthesiology / Animals / Aorta / Aortic stenosis / Biology and Life Sciences / Blood pressure / Body weight / Bromodeoxyuridine / Cerebral infarction / Chemokine receptors / Chemokines / Congestive heart failure / Constrictions / CX3C Chemokine Receptor 1 - metabolism / CX3CR1 protein / Cytokines / Cytokines - metabolism / Development and progression / Disease Models, Animal / Female / Flow cytometry / Fluorescence / Health aspects / Heart attacks / Heart enlargement / Heart failure / Heart rate / Hospitals / Hypertension / Hypertrophy / Hypertrophy, Left Ventricular - immunology / Hypertrophy, Left Ventricular - metabolism / Immune response / Immune system / Immunomodulation / Inflammation / Intensive care / Interleukins / Internal medicine / Intubation / Isoflurane / Laboratories / Leukocytes (neutrophilic) / Ligands / Macrophages / Macrophages - metabolism / Medical materials / Medicine / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Monocyte chemoattractant protein / Monocyte chemoattractant protein 1 / Monocytes / Morbidity / Myocardial infarction / Myocardium / Overloading / Research and Analysis Methods / Risk factors / Stenosis / Stroke / Stroke volume / Therapeutic targets / Tubes / Ventricle / Ventricular Dysfunction, Left - immunology / Ventricular Dysfunction, Left - metabolism / Ventricular Remodeling