| Autor: |
Namrita Kaur, Andrea Ruiz-Velasco, Rida Raja, Gareth Howell, Jessica M. Miller, Riham R.E. Abouleisa, Qinghui Ou, Kimberly Mace, Susanne S. Hille, Norbert Frey, Pablo Binder, Craig P. Smith, Helene Fachim, Handrean Soran, Eileithyia Swanton, Tamer M.A. Mohamed, Oliver J. Müller, Xin Wang, Jonathan Chernoff, Elizabeth J. Cartwright, Wei Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 3, Pp 103973- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2022.103973 |
| Popis: |
Summary: Myocardial inflammation contributes to cardiomyopathy in diabetic patients through incompletely defined underlying mechanisms. In both human and time-course experimental samples, diabetic hearts exhibited abnormal ER, with a maladaptive shift over time in rodents. Furthermore, as a cardiac ER dysfunction model, mice with cardiac-specific p21-activated kinase 2 (PAK2) deletion exhibited heightened myocardial inflammatory response in diabetes. Mechanistically, maladaptive ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) is a novel transcriptional regulator of cardiac high-mobility group box-1 (HMGB1). Cardiac stress-induced release of HMGB1 facilitates M1 macrophage polarization, aggravating myocardial inflammation. Therapeutically, sequestering the extracellular HMGB1 using glycyrrhizin conferred cardioprotection through its anti-inflammatory action. Our findings also indicated that an intact cardiac ER function and protective effects of the antidiabetic drug interdependently attenuated the cardiac inflammation-induced dysfunction. Collectively, we introduce an ER stress-mediated cardiomyocyte-macrophage link, altering the macrophage response, thereby providing insight into therapeutic prospects for diabetes-associated cardiac dysfunction. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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