Role of hypothalamic microglial activation on ventricular arrhythmias in stress cardiomyopathy
Background: Current stress cardiomyopathy (SCM) has a high incidence in older adults, and the theories revolve mostly around "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system (CNS) in the pathogenesis of stress cardiomyopathy remains unknown. Methods: We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. To create a SCM model, male Sprague-Dawley (SD) rats were immobilized for 6 hours every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography were measured to verify the changes in cardiac structure and function in rats with stress cardiomyopathy. RNA sequencing was measured to explore the changes in the hypothalamus of stress cardiomyopathy. In addition, brain and heart tissues were extracted to detect microglial activation and sympathetic activity. Results: (1) Immobilization stress successfully induced SCM in SD rats. (2) Microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickened and an increased in the number of branches and specifically enriched at PVN. (3) In SCM, microglia in the PVN increased central and peripheral cardiac sympathetic activity by increasing the expression of neuroinflammatory factors. (4) It is possible that inhibiting microglia activation could suppress central and heart sympathetic activity and increase the cardiac electrical stability in SCM rats. Conclusions: Immobilization stress induced SCM in SD rats can activate hypothalamic microglia, and the activated microglia are specifically enriched at PVN, which can increase the central and peripheral sympathetic nerve activity by regulating the expression of neuro-inflammatory factor, mediate left heart dysfunction and increase the susceptibility to ventricular fibrillation. Overall design: To investigate the role of PVN microglial cell activation in stress cardiomyopathy, we established a rat model of stress cardiomyopathy using immobilized stress, and microglial cells can be inhibited by minocycline. We collected PVN (the experiment was divided into three groups: model, minocycline, and control) for RNA- seq, comparing changes in gene expression in the RNA-seq data