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 endoplasmic reticulum (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 anti-diabetic 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.
|Early online date||23 Feb 2022|
|Publication status||Published - 23 Feb 2022|
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A study of 'Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy'. Kaur et al.
Liu, W. (Creator), Mendeley Data, 16 May 2022
DOI: 10.17632/b5y5kvjdtt.1, https://data.mendeley.com/datasets/b5y5kvjdtt