Stimulation of the Beta2 Adrenergic Receptor at Reperfusion Limits Myocardial Reperfusion Injury via an Interleukin-10-Dependent Anti-Inflammatory Pathway in the Spleen

Circulation Journal : Official Journal of the Japanese Circulation Society
Yikui TianZequan Yang

Abstract

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, phosp...Continue Reading

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Citations

Jan 4, 2019·Circulation Research·Gerd Heusch
Mar 3, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·YanHua WangYiDeng Jiang
Dec 7, 2020·The Journal of Surgical Research·Aimee ZhangZequan Yang
Dec 17, 2019·The Journal of Thoracic and Cardiovascular Surgery·Eric J CharlesZequan Yang
May 1, 2021·Cells·Anne-Sophie Colombe, Guillaume Pidoux
May 18, 2021·Frontiers in Cardiovascular Medicine·Niek J PluijmertPaul H A Quax
Aug 28, 2021·Micromachines·Arsalan Ul HaqFabio De Matteis

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