Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Acta Pharmacologica Sinica volume 44, pages 1350–1365 (2023)Cite this 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The differences in transcriptional expression patterns between β-AR agonist (ISO) and α1-AR agonist (PE) treatment.
Fig. 2: Functional enrichment analysis of differentially expressed genes in time series after ISO and PE treatment.
Fig. 3: Differences between the inflammatory cell infiltration induced by ISO and PE.
Fig. 4: Expression analysis of genes associated with neutrophils after ISO and PE treatment.
Fig. 5: PE treatment activates the NF-κB pathway.
Fig. 6: Inhibition of NF-κB significantly reduced inflammatory response after PE treatment.
Fig. 7: Combined analysis of transcriptome and proteome after ISO and PE treatment.
Fig. 8: PE causes metabolic pathway downregulation.
Fig. 9: Illustration of the differences in inflammatory responses between α1-AR and β-AR activation.

Similar content being viewed by others

Data availability

The RNA-seq data are available in the GEO database with accession number GSE211134. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [67] partner repository with the dataset identifier PXD036011.

References

  1. Scott-Solomon E, Boehm E, Kuruvilla R. The sympathetic nervous system in development and disease. Nat Rev Neurosci. 2021;22:685–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hering D, Lachowska K, Schlaich M. Role of the sympathetic nervous system in stress-mediated cardiovascular disease. Curr Hypertens Rep. 2015;17:80.

    Article  PubMed  Google Scholar 

  3. O’Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2014;66:308–33.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kivimäki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol. 2018;15:215–29.

    Article  PubMed  Google Scholar 

  5. Jensen BC, OʼConnell TD, Simpson PC. Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation. J Cardiovasc Pharmacol. 2014;63:291–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wachter SB, Gilbert EM. Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application. Cardiology. 2012;122:104–12.

    Article  CAS  PubMed  Google Scholar 

  7. Baker AJ. Adrenergic signaling in heart failure: a balance of toxic and protective effects. Pflug Arch. 2014;466:1139–50.

    Article  CAS  Google Scholar 

  8. do Vale GT, Ceron CS, Gonzaga NA, Simplicio JA, Padovan JC. Three generations of β-blockers: history, class differences and clinical applicability. Curr Hypertens Rev. 2019;15:22–31.

    Article  PubMed  Google Scholar 

  9. Wright JM, Musini VM, Gill R. First-line drugs for hypertension. Cochrane Database Syst Rev. 2018;4:Cd001841.

    PubMed  Google Scholar 

  10. Myagmar BE, Flynn JM, Cowley PM, Swigart PM, Montgomery MD, Thai K, et al. Adrenergic receptors in individual ventricular myocytes: the Beta-1 and Alpha-1B are in all cells, the Alpha-1A is in a subpopulation, and the Beta-2 and Beta-3 are mostly absent. Circ Res. 2017;120:1103–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Motiejunaite J, Amar L, Vidal-Petiot E. Adrenergic receptors and cardiovascular effects of catecholamines. Ann Endocrinol. 2021;82:193–7.

    Article  Google Scholar 

  12. Vonderlin N, Siebermair J, Kaya E, Köhler M, Rassaf T, Wakili R. Critical inflammatory mechanisms underlying arrhythmias. Herz. 2019;44:121–9.

    Article  CAS  PubMed  Google Scholar 

  13. Ong SB, Hernández-Reséndiz S, Crespo-Avilan GE, Mukhametshina RT, Kwek XY, Cabrera-Fuentes HA, et al. Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol Ther. 2018;186:73–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Murphy SP, Kakkar R, McCarthy CP, Januzzi JL Jr. Inflammation in heart failure: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75:1324–40.

    Article  PubMed  Google Scholar 

  15. Singh T, Khan H, Gamble DT, Scally C, Newby DE, Dawson D. Takotsubo syndrome: pathophysiology, emerging concepts, and clinical implications. Circulation. 2022;145:1002–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xiao H, Li H, Wang JJ, Zhang JS, Shen J, An XB, et al. IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. Eur Heart J. 2018;39:60–9.

    Article  CAS  PubMed  Google Scholar 

  17. Xin JZ, Wu JM, Hu GM, Gu HJ, Feng YN, Wang SX, et al. α(1)-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation. Acta Pharmacol Sin. 2020;41:311–8.

    Article  CAS  PubMed  Google Scholar 

  18. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12:357–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS: A J Integr Biol. 2012;16:284–7.

    Article  CAS  Google Scholar 

  21. Cox J, Hein MY, Luber CA, Paron I, Nagaraj N, Mann M. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol Cell Proteom. 2014;13:2513–26.

    Article  CAS  Google Scholar 

  22. Bruderer R, Bernhardt OM, Gandhi T, Miladinović SM, Cheng LY, Messner S, et al. Extending the limits of quantitative proteome profiling with data-independent acquisition and application to acetaminophen-treated three-dimensional liver microtissues. Mol Cell Proteom. 2015;14:1400–10.

    Article  CAS  Google Scholar 

  23. Tie L, Xiao H, Wu DL, Yang Y, Wang P. A brief guide to good practices in pharmacological experiments: Western blotting. Acta Pharmacol Sin. 2021;42:1015–7.

    Article  CAS  PubMed  Google Scholar 

  24. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–d13.

    Article  CAS  PubMed  Google Scholar 

  25. Xin JZ, Wu JM, Hu GM, Gu HJ, Feng YN, Wang SX, et al. α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation. Acta Pharmacol Sin. 2020;41:311–8.

    Article  CAS  PubMed  Google Scholar 

  26. Lafuse WP, Wozniak DJ, Rajaram MVS. Role of cardiac macrophages on cardiac inflammation, fibrosis and tissue repair. Cells. 2020;10:51.

  27. De Larco JE, Wuertz BR, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res. 2004;10:4895–900.

    Article  PubMed  Google Scholar 

  28. Rosales C. Neutrophil: a cell with many roles in inflammation or several cell types. Front Physiol. 2018;9:113.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006;354:610–21.

    Article  CAS  PubMed  Google Scholar 

  30. Capucetti A, Albano F, Bonecchi R. Multiple roles for chemokines in neutrophil biology. Front Immunol. 2020;11:1259.

  31. Hu N, Westra J, Rutgers A, Doornbos-Van der Meer B, Huitema MG, Stegeman CA, et al. Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration. Arthritis Res Ther. 2011;13:R201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nolan KF, Strong V, Soler D, Fairchild PJ, Cobbold SP, Croxton R, et al. IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals. J Immunol. 2004;172:2201.

    Article  CAS  PubMed  Google Scholar 

  33. Das T, Chen Z, Hendriks RW, Kool M. A20/tumor necrosis factor α-induced protein 3 in immune cells controls development of autoinflammation and autoimmunity: lessons from mouse models. Front Immunol. 2018;9:104.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Regan-Komito D, Valaris S, Kapellos TS, Recio C, Taylor L, Greaves DR, et al. Absence of the non-signalling chemerin receptor CCRL2 exacerbates acute inflammatory responses in vivo. Front Immunol. 2017;8:1621.

  35. Mandeville I, Aubin J, LeBlanc M, Lalancette-Hébert M, Janelle MF, Tremblay GM, et al. Impact of the loss of Hoxa5 function on lung alveogenesis. Am J Pathol. 2006;169:1312–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Becker F, Potepalov S, Shehzahdi R, Bernas M, Witte M, Abreo F, et al. Downregulation of FoxC2 increased susceptibility to experimental colitis: influence of lymphatic drainage function? Inflamm Bowel Dis. 2015;21:1282–96.

    PubMed  Google Scholar 

  37. George T, Bell M, Chakraborty M, Siderovski DP, Giembycz MA, Newton R. Protective roles for RGS2 in a mouse model of house dust mite-induced airway inflammation. PLoS One. 2017;12:e0170269.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Immler R, Simon SI, Sperandio M. Calcium signalling and related ion channels in neutrophil recruitment and function. Eur J Clin Invest. 2018;48:e12964.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Béguin P, Nagashima K, Mahalakshmi RN, Vigot R, Matsunaga A, Miki T, et al. BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis. J Cell Biol. 2014;205:233–49.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Maguire O, O’Loughlin K, Minderman H. Simultaneous assessment of NF-κB/p65 phosphorylation and nuclear localization using imaging flow cytometry. J Immunol Methods. 2015;423:3–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020;11:102.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Liu Y, Beyer A, Aebersold R. On the dependency of cellular protein levels on mRNA abundance. Cell. 2016;165:535–50.

    Article  CAS  PubMed  Google Scholar 

  44. Dewenter M, Pan J, Knödler L, Tzschöckel N, Henrich J, Cordero J, et al. Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha(1)-adrenoceptors to early cardiac stress responses. Basic Res Cardiol. 2022;117:15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair. J Athl Train. 2006;41:457–65.

    PubMed  PubMed Central  Google Scholar 

  46. Watanabe S, Alexander M, Misharin AV, Budinger GRS. The role of macrophages in the resolution of inflammation. J Clin Invest. 2019;129:2619–28.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kim Y, Nurakhayev S, Nurkesh A, Zharkinbekov Z, Saparov A. Macrophage polarization in cardiac tissue repair following myocardial infarction. Int J Mol Sci. 2021;22:2715.

  48. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, et al. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med. 2003;9:1506–12.

    Article  CAS  PubMed  Google Scholar 

  49. Schioppa T, Sozio F, Barbazza I, Scutera S, Bosisio D, Sozzani S, et al. Molecular basis for CCRL2 regulation of leukocyte migration. Front Cell Dev Biol. 2020;8:615031.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sjögren B, Parra S, Atkins KB, Karaj B, Neubig RR. Digoxin-mediated upregulation of RGS2 protein protects against cardiac injury. J Pharmacol Exp Ther. 2016;357:311–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Li HM, Li KY, Xing Y, Tang XX, Yang DM, Dai XM, et al. Phenylephrine attenuated sepsis-induced cardiac inflammation and mitochondrial injury through an effect on the PI3K/Akt signaling pathway. J Cardiovasc Pharmacol. 2019;73:186–94.

    Article  CAS  PubMed  Google Scholar 

  52. Li PL, Liu H, Chen GP, Li L, Shi HJ, Nie HY, et al. STEAP3 (six-transmembrane epithelial antigen of prostate 3) inhibits pathological cardiac hypertrophy. Hypertension. 2020;76:1219–30.

    Article  CAS  PubMed  Google Scholar 

  53. Kumar S, Wang G, Liu W, Ding W, Dong M, Zheng N, et al. Hypoxia-induced mitogenic factor promotes cardiac hypertrophy via calcium-dependent and hypoxia-inducible factor-1α mechanisms. Hypertension. 2018;72:331–42.

    Article  CAS  PubMed  Google Scholar 

  54. Yamamura S, Izumiya Y, Araki S, Nakamura T, Kimura Y, Hanatani S, et al. Cardiomyocyte Sirt (Sirtuin) 7 ameliorates stress-induced cardiac hypertrophy by interacting with and deacetylating GATA4. Hypertension. 2020;75:98–108.

    Article  CAS  PubMed  Google Scholar 

  55. Soehnlein O, Lindbom L, Weber C. Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood. 2009;114:4613–23.

    Article  CAS  PubMed  Google Scholar 

  56. Silvestre-Roig C, Braster Q, Ortega-Gomez A, Soehnlein O. Neutrophils as regulators of cardiovascular inflammation. Nat Rev Cardiol. 2020;17:327–40.

    Article  PubMed  Google Scholar 

  57. Schiattarella GG, Rodolico D, Hill JA. Metabolic inflammation in heart failure with preserved ejection fraction. Cardiovasc Res. 2021;117:423–34.

    Article  CAS  PubMed  Google Scholar 

  58. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013;496:238–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem. 2017;292:16804–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Amin JK, Xiao L, Pimental DR, Pagano PJ, Singh K, Sawyer DB, et al. Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol. 2001;33:131–9.

    Article  CAS  PubMed  Google Scholar 

  61. Xiao L, Pimentel DR, Wang J, Singh K, Colucci WS, Sawyer DB. Role of reactive oxygen species and NAD(P)H oxidase in alpha(1)-adrenoceptor signaling in adult rat cardiac myocytes. Am J Physiol Cell Physiol. 2002;282:C926–34.

    Article  CAS  PubMed  Google Scholar 

  62. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin Invest. 2018;128:3716–26.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Strassheim D, Dempsey EC, Gerasimovskaya E, Stenmark K, Karoor V. Role of inflammatory cell subtypes in heart failure. J Immunol Res. 2019;2019:2164017.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Redfors B, Vedad R, Angerås O, Råmunddal T, Petursson P, Haraldsson I, et al. Mortality in takotsubo syndrome is similar to mortality in myocardial infarction—a report from the SWEDEHEART registry. Int J Cardiol. 2015;185:282–9.

    Article  PubMed  Google Scholar 

  66. Isogai T, Matsui H, Tanaka H, Fushimi K, Yasunaga H. Early β-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy. Heart. 2016;102:1029–35.

    Article  PubMed  Google Scholar 

  67. Perez-Riverol Y, Bai J, Bandla C, García-Seisdedos D, Hewapathirana S, Kamatchinathan S, et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidence. Nucleic Acids Res. 2022;50:D543–d52.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Beijing Municipal Natural Science Foundation [grant number 7191013 to EDD], the National Key R&D Program of China [2021YFF0501401 to HX; 2021YFF1200500 to ZYL], the National Natural Science Foundation of China [grant numbers 82030072, 81822003 to HX; 81830009 to YYZ; 82100280 to JMW], the Haihe Laboratory of Cell Ecosystem Innovation Fund [grant number HH22KYZX0047 to EDD], and the Key Clinical Projects of Peking University Third Hospital [grant number BYSYZD2019022 to HX]. This work was partly supported by grants from Peking-Tsinghua Center for Life Sciences.

Author information

Author notes

  1. These authors contributed equally: Di Zhang, Ming-ming Zhao

  2. These authors jointly supervised this work: Er-dan Dong, Zhi-yuan Li, Han Xiao

Authors and Affiliations

  1. Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China

    Di Zhang, Ji-qi Shao & Zhi-yuan Li

  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

    Ming-ming Zhao, Ji-min Wu, Rui Wang, You-yi Zhang, Er-dan Dong & Han Xiao

  3. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China

    Gang Xue & Zhi-yuan Li

  4. Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Yan-bo Xue

Authors
  1. Di Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-ming Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ji-min Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gang Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan-bo Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ji-qi Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. You-yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Er-dan Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhi-yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Han Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HX and JMW conceived and designed the research; MMZ, DZ, and JMW performed the research; DZ performed the data curation and formal analysis; RW and YBX helped with the experiments; GX and JQS helped with the data analysis; DZ, JMW, HX, and ZYL wrote and edited the manuscript; HX, ZYL, YYZ, and EDD supervised the Project. All authors approved the manuscript.

Corresponding authors

Correspondence to Er-dan Dong, Zhi-yuan Li or Han Xiao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, D., Zhao, Mm., Wu, Jm. et al. Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and β-adrenergic receptors activation. Acta Pharmacol Sin 44, 1350–1365 (2023). https://doi.org/10.1038/s41401-022-01048-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41401-022-01048-5

Keywords

This article is cited by

Search

Advanced search

Quick links