Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment
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 chara...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
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| Series: | JACC: Basic to Translational Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X19301962 |
| _version_ | 1818556385279868928 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ricardo A. García, PhD |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-13T23:46:40Z |
| format | Article |
| id | doaj.art-87187fce26ae464386af76218484bf38 |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-12-13T23:46:40Z |
| publishDate | 2019-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-87187fce26ae464386af76218484bf382022-12-21T23:26:56ZengElsevierJACC: Basic to Translational Science2452-302X2019-12-0148905920Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist TreatmentRicardo A. García, PhD0Bruce R. Ito, PhD1John A. Lupisella, MSc2Nancy A. Carson, BSc3Mei-Yin Hsu, MSc4Gayani Fernando, MSc5Madeleine Heroux, PhD6Michel Bouvier, PhD7Elizabeth Dierks, PhD8Ellen K. Kick, PhD9David A. Gordon, PhD10Jian Chen, PhD11Gabe Mintier, BSc12Marilyn Carrier, PhD13Stéphane St-Onge, MSc14Himanshu Shah, MSc15Jordan Towne, BSc16Marcela Sotelo Bucardo, BSc17Xiuying Ma, PhD18Carol S. Ryan, BSc19Nicholas R. Wurtz, PhD20Jacek Ostrowski, PhD21Francisco J. Villarreal, MD, PhD22Department 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.Department of Medicine, University of California San Diego, San Diego, CaliforniaDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, CanadaInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, CanadaDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, CanadaInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, CanadaDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Medicine, University of California San Diego, San Diego, CaliforniaDepartment of Medicine, University of California San Diego, San Diego, CaliforniaDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Cardiovascular and Fibrosis Drug Discovery, Bristol-Myers Squibb Company, Pennington, New JerseyDepartment of Medicine, University of California San Diego, San Diego, CaliforniaSummary: 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 infarctionhttp://www.sciencedirect.com/science/article/pii/S2452302X19301962 |
| spellingShingle | 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 Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment JACC: Basic to Translational Science |
| title | Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment |
| title_full | Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment |
| title_fullStr | Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment |
| title_full_unstemmed | Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment |
| title_short | Preservation of Post-Infarction Cardiac Structure and Function via Long-Term Oral Formyl Peptide Receptor Agonist Treatment |
| title_sort | preservation of post infarction cardiac structure and function via long term oral formyl peptide receptor agonist treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X19301962 |
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