Abstract
Inflammation urges most of the characteristics of plaques involved in the pathogenesis of myocardial ischemia/reperfusion injury (MI/RI). In addition, inflammatory signaling pathways not only mediate the properties of plaques that precipitate ischemia/reperfusion (I/R) but also influence the clinical consequences of the post-infarction remodeling and heart failure. Here, we studied whether Ginkgolide B (GB), an effective anti-inflammatory monomer, improved MI/RI via suppression of inflammation. Left anterior descending (LAD) coronary artery induced ischemia/reperfusion (I/R) of rats or A20 silencing mice, as well as hypoxia/reoxygenation (H/R) induced damages of primary cultured rat neonatal ventricular myocytes or A20 silencing ventricular myocytes, respectively, served as MI/RI model in vivo and in vitro to discuss the anti-I/R injury properties of GB. We found that GB significantly alleviated the symptoms of MI/RI evidently by reducing infarct size, preventing ultrastructural changes of myocardium, depressing Polymorphonuclears (PMNs) infiltration, lessening histopathological damage and suppressing the excessive inflammation. Further study demonstrated that GB remarkably inhibited NF-κB p65 subunit translocation, IκB-α phosphorylation, IKK-β activity, as well as the downstream inflammatory cytokines and proteins expressions via zinc finger protein A20. In conclusion, GB could alleviate MI/RI-induced inflammatory response through A20-NF-κB signal pathway, which may give us new insights into the preventive strategies for MI/RI disease.
Highlights
Myocardial ischemia/reperfusion injury (MI/RI) with high morbidity and mortality rates has become one of the decisive factors for the events of cardiovascular diseases [1, 2]
Ginkgolide B (GB) Reduced Infarct Size in myocardial ischemia/reperfusion injury (MI/RI) Rats As the results shown in Figure 2B, infarct size in the I/R group was 41.5 ± 4.9% (P < 0.01 vs. control group), whereas 8, 16, 32 mg/kg GB decreased infarct size to 32.4 ± 3.7%, 25.2 ± 5.0% and 21.3 ± 4.0% (P < 0.01), respectively, compared with the I/R group
The ventricular myocytes in other groups were preincubated with pGPU6/Hygro-A20 and no A20 expressed after transfection. This is the first investigation studied on MI/RI both in vivo and in vitro to examine whether GB played a vital role in the whole pathological process of MI/RI, whether GB regulated the expression of A20 in response to H/R injury, and whether NF-κB signal pathway was heavily involved in the whole pathogenesis
Summary
Myocardial ischemia/reperfusion injury (MI/RI) with high morbidity and mortality rates has become one of the decisive factors for the events of cardiovascular diseases [1, 2]. The mechanisms of MI/RI refer to a series of complicated pathological processes, including inflammatory response, calcium overload, complement activation, cell autophagy, and apoptosis [3]. It has repeatedly been shown that the earliest phases of ischemia/reperfusion (I/R) are dominated by an acute inflammatory response. The mechanisms driving this acute and robust inflammatory response are still unknown. Over the last decades, it has become increasingly clear that Zinc finger protein A20 is considered to be a pivotal link to the inflammation throughout the whole pathological process of myocardial ischemia/reperfusion induced tissue injury [4]. No data have been published focused on the role of A20 in pathogenesis of MI/RI
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