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

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

  • Acta Pharmacol Sin. 2023 Feb 3. doi: 10.1038/s41401-022-01048-5.
Di Zhang # 1,  Ming-Ming Zhao # 2,  Ji-Min Wu 2,  Rui Wang 2,  Gang Xue 3,  Yan-Bo Xue 4,  Ji-Qi Shao 1,  You-Yi Zhang 2,  Er-Dan Dong 5,  Zhi-Yuan Li 6 7,  Han Xiao 8
Affiliations

Affiliations

  • 1 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • 2 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research; Haihe Laboratory of Cell Ecosystem, Beijing, 100191, China.
  • 3 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • 4 Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
  • 5 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research; Haihe Laboratory of Cell Ecosystem, Beijing, 100191, China. donged@bjmu.edu.cn.
  • 6 Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. zhiyuanli@pku.edu.cn.
  • 7 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. zhiyuanli@pku.edu.cn.
  • 8 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research; Haihe Laboratory of Cell Ecosystem, Beijing, 100191, China. xiaohan@bjmu.edu.cn.
  • # Contributed equally.
PMID: 36737635 DOI: 10.1038/s41401-022-01048-5
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.

Keywords

acute sympathetic stress; adrenergic receptors; cardiac inflammation; proteomics; transcriptomics.

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