Stimulation of the Beta2 adrenergic receptor at reperfusion limits myocardial reperfusion injury via an interleukin-10-dependent anti-inflammatory pathway in the spleen

Yikui Tian, Bin Miao, Eric J. Charles, Di Wu, Irving L. Kron, Brent A. French, Zequan Yang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: In addition to the airway-relaxing effects, β2 adrenergic receptor (β2AR) agonists are also found to have broad anti-inflammatory effects. The current study was conducted to define the role of β2AR agonists in limiting myocardial ischemia/ reperfusion injury (IRI). Methods and Results: Adult male wild-type (WT) and interleukin (IL)-10 knockout (KO) mice underwent a 40-min left coronary artery ligation and 60-min reperfusion. A selective β2AR agonist, Clenbuterol, at doses of 0.1 μg or 1 μg/g weight i.v. 5 min before reperfusion, significantly reduced myocardial infarct size (IS) by 28% and 39% (vs. control, P<0.05) in WT mice respectively, but had no protective effect in IL-10 KO mice. Inhalational therapy with nebulized Clenbuterol, Albuterol, Salmeterol or Arformoterol immediately before ischemia significantly reduced IS (P<0.05) in WT mice. Splenectomy similarly reduced IS as Clenbuterol-treated mice, but intravenous Clenbuterol did not further reduce IS in splenectomized mice. In splenectomized WT mice, acute transfer of isolated splenocytes, not the Clenbuterol-pretreated splenocytes, restored the myocardial IS to the level of intact mice. Intravenous Clenbuterol significantly increased splenic protein levels of β2AR, phosphorylated Akt and IL-10 and plasma IL-10, and inhibited the expression of pro-inflammatory mRNAs. Conclusions: Both intravenous and inhalational β2AR agonists exert a cardioprotective effect against IRI by activating the anti-inflammatory β2AR-IL-10 pathway.

Original languageEnglish (US)
Pages (from-to)2829-2836
Number of pages8
JournalCirculation Journal
Volume82
Issue number11
DOIs
StatePublished - 2018

Keywords

  • Clenbuterol
  • Heart
  • Ischemia/reperfusion
  • Myocardial infarction
  • βAR

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Stimulation of the Beta2 adrenergic receptor at reperfusion limits myocardial reperfusion injury via an interleukin-10-dependent anti-inflammatory pathway in the spleen'. Together they form a unique fingerprint.

Cite this