Author + information
- Received August 25, 2017
- Revision received October 11, 2017
- Accepted December 19, 2017
- Published online April 30, 2018.
- Bindiya Patel, PhDa,
- Shyam S. Bansal, PhDa,
- Mohamed Ameen Ismahil, PhDa,
- Tariq Hamid, PhDa,
- Gregg Rokosh, PhDa,
- Matthias Mack, MDb and
- Sumanth D. Prabhu, MDa,c,∗ ()
- aDepartment of Medicine, Division of Cardiovascular Disease and Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, Alabama
- bDepartment of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
- cMedical Service, Birmingham VAMC, Birmingham, Alabama
- ↵∗Address for correspondence:
Dr. Sumanth D. Prabhu, Division of Cardiovascular Disease, University of Alabama at Birmingham, 311 Tinsley Harrison Tower, 1900 University Boulevard, Birmingham, Alabama 35294-0006.
• Hypothesis: CCR2+ monocyte-derived cardiac macrophages are required for adverse LV remodeling, cardiac T-cell expansion, and the transition to HF following pressure overload.
• The imposition of pressure overload via TAC resulted in the early up-regulation of CCL2, CCL7, and CCL12 chemokines in the LV, increased Ly6ChiCCR2+ monocytes in the blood, and augmented CCR2+ infiltrating macrophages in the heart.
• Specific and circumscribed inhibition of CCR2+ monocytes and macrophages early during pressure overload reduced pathological hypertrophy, fibrosis, and systolic dysfunction during the late phase of pressure overload.
• The early expansion of CCR2+ macrophages after pressure overload was required for long-term cardiac T-cell expansion.
• CCR2+ monocytes/macrophages may represent key targets for immunomodulation to delay or prevent HF in pressure-overload states.
Although chronic inflammation is a central feature of heart failure (HF), the immune cell profiles differ with different underlying causes. This suggests that for immunomodulatory therapy in HF to be successful, it needs to be tailored to the specific etiology. Here, the authors demonstrate that monocyte-derived C-C chemokine receptor 2 (CCR2)+ macrophages infiltrate the heart early during pressure overload in mice, and that blocking this response either pharmacologically or with antibody-mediated CCR2+ monocyte depletion alleviates late pathological left ventricular remodeling and dysfunction, T-cell expansion, and cardiac fibrosis. Hence, suppression of CCR2+ monocytes/macrophages may be an important immunomodulatory therapeutic target to ameliorate pressure-overload HF.
This work was supported by National Institutes of Health grant R01HL125735 and a VA Merit Award I01BX002706 (both to Dr. Prabhu). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received August 25, 2017.
- Revision received October 11, 2017.
- Accepted December 19, 2017.