JAK2/STAT3 pathway mediates beneficial effects of pterostilbene on cardiac contractile and electrical function in the setting of myocardial reperfusion injury

Title:

JAK2/STAT3 pathway mediates beneficial effects of pterostilbene on cardiac contractile and electrical function in the setting of myocardial reperfusion injury

Creator:

Li, Sanjun, Wang, Hong, and Zhou, Yuxuan

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:56df09c8-8037-4e76-9804-0e8cd109c8af
uuid:56df09c8-8037-4e76-9804-0e8cd109c8af
doi:10.33549/physiolres.934919

Subject:

arrhythmia, ischemia, reperfusion, signaling pathway, pterostilbene, and JAK2/STAT3

Type:

model:article and TEXT

Format:

počítač and online zdroj

Description:

Contractile dysfunction and fatal arrhythmias are the hallmarks of myocardial ischemia/reperfusion (I/R) injury. Pterostilbene has notable cardioprotective effects, but its main mechanisms are not fully understood. Here, we investigated the effect of PTE on myocardial hemodynamics, arrhythmias, inflammatory/oxidative responses, and the causal role of the JAK2/STAT3 pathway in rats with acute myocardial I/R injury. Sixty male 7-8 months Sprague-Dawley rats (n=10/each group) experienced in vivo model of myocardial I/R injury through 40-min LAD coronary artery occlusion and subsequent 24-h reperfusion. PTE at concentrations of 5 and 25 mg/kg was intraperitoneally administered to rats five min before reperfusion. Cardiac hemodynamics, reperfusion-induced ventricular arrhythmias, infarct size, inflammatory cytokines, oxidative stress markers, the activity of the JAK2/STAT3 pathway were measured as the endpoints. Administration of PTE to I/R-injured rats recovered myocardial contractile function and reduced infarct size and ventricular arrhythmias counts and incidence in a dosedependent manner. PTE at 25 mg/kg significantly and more potently reduced the levels of inflammatory mediators NF-κB, TNF-α, and IL-1β, suppressed intracellular ROS production, augmented the activity of glutathione, and manganesesuperoxide dismutase, and upregulated the JAK2 and STAT3 phosphorylation. Importantly, pretreatment of rats with Ag490 as a JAK2 inhibitor significantly abolished the cardioprotective and signaling effects of PTE in I/R rats. PTE exerts significant protective effects on reducing arrhythmias and myocardial infarction and enhancing cardiac function by stimulating JAK2/STAT3-related suppression of inflammatory and oxidative reactions in the I/R injury setting.

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Coverage:

489-499

Source:

Physiological research | 2022 Volume:71 | Number:4

Harvested from:

CDK

Metadata only:

false