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Updated: Nov 22, 2025
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
CX3CR1 is a prerequisite for the development of cardiac hypertrophy and left ventricular dysfunction in mice upon
Christina Katharina Weisheit1, Jan Lukas Kleiner1, Maria Belen Rodrigo1
1Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Insights
The CX3CL1/CX3CR1 axis is crucial for heart failure development. Blocking this pathway, specifically CX3CR1 (fractalkine receptor), shows cardioprotective effects in pressure-overload induced heart failure.
Area of Science:
- Cardiovascular Disease Immunology
- Molecular Mechanisms of Heart Failure
- Inflammation and Immunity
Background:
- The CX3CL1/CX3CR1 axis is vital for leukocyte trafficking and implicated in cardiovascular disease pathology.
- Cardiac immune responses vary with disease etiology, necessitating investigation for targeted immunomodulatory therapies in heart failure.
- Understanding immune patterns in pressure overload-induced left ventricular (LV) hypertrophy is key for developing effective treatments.
Purpose of the Study:
- To investigate the role of the fractalkine receptor CX3CR1 in the development of cardiac hypertrophy and dysfunction following pressure overload.
- To compare the cardiac immune response in wild-type mice versus CX3CR1-deficient mice subjected to transverse aortic constriction (TAC).
Main Methods:
- Utilized a mouse model of transverse aortic constriction (TAC) to induce pressure overload and left ventricular hypertrophy.
- Compared cardiac structure, function, and immune cell infiltration between wild-type C57BL/6 mice and CX3CR1-deficient mice.
- Analyzed immune cell populations (neutrophils, Ly6C(high) and Ly6C(low) macrophages) and cytokine expression profiles.
Main Results:
- CX3CR1 deficiency significantly reduced LV hypertrophy and preserved cardiac function in response to TAC-induced pressure overload.
- Absence of CX3CR1 shifted the immune response from a Ly6C(low) macrophage-dominated profile to an early pro-inflammatory response involving neutrophils and Ly6C(high) macrophages.
- CX3CR1-deficient mice exhibited altered cytokine expression patterns and reduced infiltration of Ly6C(high) monocytes driven by CCL2.
Conclusions:
- CX3CR1 is essential for the development of cardiac hypertrophy and left ventricular dysfunction under pressure overload conditions.
- CX3CR1 deficiency confers significant cardioprotective effects by modulating the early inflammatory response.
- Targeting the CX3CR1 pathway represents a potential immunomodulatory therapeutic strategy for mitigating pressure-overload induced heart failure.
Abstract:
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 Ly6Clow macrophages changed to an early pro-inflammatory immune response driven by neutrophils, Ly6Chigh macrophages and altered cytokine expression pattern in CX3CR1 deficient mice. In this early inflammatory phase of LV hypertrophy Ly6Chigh 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.
