Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and β-adrenergic receptors activation

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.