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Journal article
Small molecule disruption of G protein beta gamma subunit signaling reprograms human macrophage phenotype and prevents autoimmune myocarditis in rats
PloS one, v 13(7)
19 Jul 2018
PMID: 30024944
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The purpose of this study was to determine whether blocking of G protein beta gamma (G beta gamma) signaling halts heart failure (HF) progression by macrophage phenotype manipulation. Cardiac G beta gamma signaling plays a crucial role in HF pathogenesis. Previous data suggested that inhibiting G beta gamma signaling reprograms T helper cell 1 (Th1) and Th2 cytokines, suggesting that G beta gamma might be a useful drug target for treating HF. We investigated the efficacy of a small molecule G beta gamma inhibitor, gallein, in a clinically relevant, experimental autoimmune myocarditis (EAM) model of HF as well as in human macrophage phenotypes in vitro. In the myocardium of HF patients, we observed that G protein coupled receptor kinase (GRK)2 levels were down-regulated compared with healthy controls. In rat EAM, treatment with gallein effectively improved survival and cardiac function, suppressed cardiac remodeling, and further attenuated myocardial protein expression of GRK2 as well as high mobility group box (HMGB)1 and its cascade signaling proteins. Furthermore, gallein effectively inhibited M1 polarization and promoted M2 polarization in vivo in the EAM heart and in vitro in human monocyte-derived macrophages. Taken together, these data suggest that the small molecule G beta gamma inhibitor, gallein, could be an important pharmacologic therapy for HF as it can switch the phenotypic reprogramming from M1 to M2 phenotype in a rat model of EAM heart and in human macrophages.
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Details
- Title
- Small molecule disruption of G protein beta gamma subunit signaling reprograms human macrophage phenotype and prevents autoimmune myocarditis in rats
- Creators
- Vengadeshprabhu Karuppagounder - Niigata University of Pharmacy and Applied Life SciencesAnamika Bajpai - Drexel UniversityShu Meng - The University of Texas Health Science Center at HoustonSomasundaram Arumugam - Niigata University of Pharmacy and Applied Life SciencesRemya Sreedhar - Niigata University of Pharmacy and Applied Life SciencesVijayasree V. Giridharan - Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, Houston, Texas, United States of America.Ashrith Guha - Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, United States of America.Arvind Bhimaraj - Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, United States of America.Keith A. Youker - Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, United States of America.Suresh S. Palaniyandi - Henry Ford Health SystemHarry Karmouty-Quintana - The University of Texas Health Science Center at HoustonFadia Kamal - Penn State Milton S. Hershey Medical CenterKara L. Spiller - Drexel UniversityKenichi Watanabe - Niigata University of Pharmacy and Applied Life SciencesRajarajan A. Thandavarayan - Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, Texas, United States of America.
- Publication Details
- PloS one, v 13(7)
- Publisher
- Public Library Science
- Number of pages
- 16
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000439120000042
- Scopus ID
- 2-s2.0-85050521996
- Other Identifier
- 991019169535504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems