Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction.

Autor:	García RA; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA.; Department of Medicine, University of California-San Diego, San Diego, California, USA., Lupisella JA; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Ito BR; Department of Medicine, University of California-San Diego, San Diego, California, USA., Hsu MY; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Fernando G; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Carson NL; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Allocco JJ; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Ryan CS; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Zhang R; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Wang Z; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Heroux M; Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada., Carrier M; Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada., St-Onge S; Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada., Bouvier M; Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec, Canada., Dudhgaonkar S; Biocon Bristol Myers Squibb Research Center, Bangalore, India., Nagar J; Biocon Bristol Myers Squibb Research Center, Bangalore, India., Bustamante-Pozo MM; Department of Medicine, University of California-San Diego, San Diego, California, USA., Garate-Carrillo A; Department of Medicine, University of California-San Diego, San Diego, California, USA., Chen J; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Ma X; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Search DJ; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Dierks EA; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Kick EK; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Wexler RR; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Gordon DA; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Ostrowski J; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Wurtz NR; Department of Cardiovascular and Fibrosis Drug Discovery, Bristol Myers Squibb, Princeton, New Jersey, USA., Villarreal F; Department of Medicine, University of California-San Diego, San Diego, California, USA.
Jazyk:	angličtina
Zdroj:	JACC. Basic to translational science [JACC Basic Transl Sci] 2021 Aug 23; Vol. 6 (8), pp. 676-689. Date of Electronic Publication: 2021 Aug 23 (Print Publication: 2021).
DOI:	10.1016/j.jacbts.2021.07.007
Abstrakt:	Dysregulated inflammation following myocardial infarction (MI) leads to maladaptive healing and remodeling. The study characterized and evaluated a selective formyl peptide receptor 2 (FPR2) agonist BMS-986235 in cellular assays and in rodents undergoing MI. BMS-986235 activated G proteins and promoted β-arrestin recruitment, enhanced phagocytosis and neutrophil apoptosis, regulated chemotaxis, and stimulated interleukin-10 and monocyte chemoattractant protein-1 gene expression. Treatment with BMS-986235 improved mouse survival, reduced left ventricular area, reduced scar area, and preserved wall thickness. Treatment increased macrophage arginase-1 messenger RNA and CD206 receptor levels indicating a proresolution phenotype. In rats following MI, BMS-986235 preserved viable myocardium, attenuated left ventricular remodeling, and increased ejection fraction relative to control animals. Therefore, FPR2 agonism improves post-MI healing, limits remodeling and preserves function, and may offer an innovative therapeutic option to improve outcomes. Competing Interests: This work was supported by Bristol Myers Squibb (Princeton, New Jersey, USA). All authors are employees of Bristol Myers Squibb or affiliates via collaboration or contract research. (© 2021 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu