Authors: Di Zhang, Ming-ming Zhao, Ji-min Wu, Rui Wang, Gang Xue, Yan-bo Xue, Ji-qi Shao, You-yi Zhang, Er-dan Dong, Zhi-yuan Li and Han Xiao
Journal: ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/s41401-022-01048-5
Link: https://www.nature.com/articles/s41401-022-01048-5
Published: Feb 3, 2023
Document Type: Article
Abstract:
Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and β-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and β-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and β-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and β-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not β-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with β-AR overactivation. These findings provide a new therapeutic strategy that, besides using β-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.