JACC: Basic to Translational Science (Dec 2019)
Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment
- Ricardo A. García, PhD,
- Bruce R. Ito, PhD,
- John A. Lupisella, MSc,
- Nancy A. Carson, BSc,
- Mei-Yin Hsu, MSc,
- Gayani Fernando, MSc,
- Madeleine Heroux, PhD,
- Michel Bouvier, PhD,
- Elizabeth Dierks, PhD,
- Ellen K. Kick, PhD,
- David A. Gordon, PhD,
- Jian Chen, PhD,
- Gabe Mintier, BSc,
- Marilyn Carrier, PhD,
- Stéphane St-Onge, MSc,
- Himanshu Shah, MSc,
- Jordan Towne, BSc,
- Marcela Sotelo Bucardo, BSc,
- Xiuying Ma, PhD,
- Carol S. Ryan, BSc,
- Nicholas R. Wurtz, PhD,
- Jacek Ostrowski, PhD,
- Francisco J. Villarreal, MD, PhD
Affiliations
- Ricardo A. García, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey; Department of Medicine, University of California San Diego, San Diego, California; Address for correspondence: Dr. Ricardo A. Garcia, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, New Jersey 08534.
- Bruce R. Ito, PhD
- Department of Medicine, University of California San Diego, San Diego, California
- John A. Lupisella, MSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Nancy A. Carson, BSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Mei-Yin Hsu, MSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Gayani Fernando, MSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Madeleine Heroux, PhD
- Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada
- Michel Bouvier, PhD
- Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada
- Elizabeth Dierks, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Ellen K. Kick, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- David A. Gordon, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Jian Chen, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Gabe Mintier, BSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Marilyn Carrier, PhD
- Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada
- Stéphane St-Onge, MSc
- Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada
- Himanshu Shah, MSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Jordan Towne, BSc
- Department of Medicine, University of California San Diego, San Diego, California
- Marcela Sotelo Bucardo, BSc
- Department of Medicine, University of California San Diego, San Diego, California
- Xiuying Ma, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Carol S. Ryan, BSc
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Nicholas R. Wurtz, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Jacek Ostrowski, PhD
- Department of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New Jersey
- Francisco J. Villarreal, MD, PhD
- Department of Medicine, University of California San Diego, San Diego, California
- Journal volume & issue
-
Vol. 4,
no. 8
pp. 905 – 920
Abstract
Summary: Dysregulated inflammation following myocardial infarction (MI) promotes left ventricular (LV) remodeling and loss of function. Targeting inflammation resolution by activating formyl peptide receptors (FPRs) may limit adverse remodeling and progression towards heart failure. This study characterized the cellular and signaling properties of Compound 43 (Cmpd43), a dual FPR1/FPR2 agonist, and examined whether Cmpd43 treatment improves LV and infarct remodeling in rodent MI models. Cmpd43 stimulated FPR1/2-mediated signaling, enhanced proresolution cellular function, and modulated cytokines. Cmpd43 increased LV function and reduced chamber remodeling while increasing proresolution macrophage markers. The findings demonstrate that FPR agonism improves cardiac structure and function post-MI. Key Words: agonist, Compound 43, formyl peptide receptor, heart failure, myocardial infarction
