Abstract
BackgroundBlood flow restoration is a definitive therapy for salvaging the myocardium following ischemic injury. Nevertheless, the sudden restoration of blood flow to the ischemic myocardium can induce ischemia-reperfusion injury (IRI).ResultsHerein, we investigated the cardioprotective effect of remote ischemic postconditioning (RPostC) through our in vivo rat model of myocardial IRI. The study included three groups: the control group, the IRI group, and the IRI + RPostC group. Ischemia-reperfusion treatment led to an increase in the myocardial infarction area, which was inhibited by RPostC. In contrast to that in the control group, the myocardial apoptosis level was enhanced in the IRI group, whereas RPostC treatment decreased IRI-induced cellular apoptosis. Affymetrix Rat Gene 2.0 ST chip data identified a total of 265 upregulated genes and 267 downregulated genes between the IRI and IRI + RPostC groups. A group of differentially expressed noncoding RNAs (ncRNAs), such as MTA_TC0600002772.mm, MTA_TC1300002394.mm, U7 small nuclear RNA (Rnu7) and RGD7543256_1, were identified. Gene Ontology (GO) enrichment analysis indicated that the positive regulation of some molecular functions, such as GTPase activity, GTP binding, cyclic-nucleotide phosphodiesterase activity and cytokine activity, may contribute to the cardioprotective role of RPostC. Moreover, pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested the potential implication of the TNF signaling pathway and Toll-like receptor signaling pathway. Global signal transduction network analysis, co-expression network analysis and quantitative real-time polymerase chain reaction analysis further identified several core genes, including Pdgfra, Stat1, Lifr and Stfa3.ConclusionRemote ischemic postconditioning treatment can decrease IRI-mediated myocardial apoptosis by regulating multiple processes and pathways, such as GTPase activity, cytokine activity, and the TNF and Toll-like receptor signaling pathways. The potential role of the above ncRNAs and core genes in IRI-induced cardiac damage merits further study as well.
Highlights
Blood flow restoration is a definitive therapy for salvaging the myocardium following ischemic injury
We performed remote ischemic postconditioning (RPostC) treatment by three cycles of 30 s left femoral artery (LFA) occlusion/30 s reperfusion in rats that underwent ischemia-reperfusion injury (IRI), which was induced by 45 min of left anterior descending coronary artery (LAD) occlusion
We carried out a histological triphenylte-trazolium chloride (TTC) staining assay to preliminarily evaluate the impact of the ischemia/reperfusion process or RPostC treatment in rats suffering from myocardial ischemia-reperfusion injury
Summary
Blood flow restoration is a definitive therapy for salvaging the myocardium following ischemic injury. The sudden restoration of blood flow to the ischemic myocardium can induce ischemia-reperfusion injury (IRI). Ischemia-reperfusion injury (IRI) is a phenomenon in which cell metabolism and structural damage are aggravated when blood flow is restored after myocardial ischemia and reperfusion [1,2,3]. RPostC refers to the protective effect seen upon the transient ischemic treatment of distant organs or tissues before the restoration of blood flow to the ischemic area [9, 13,14,15,16]. Because RPostC avoids the clamping of coronary vessels, it achieves this myocardial protective effect through a simple and noninvasive intervention for the ischemic postconditioning of distant position and represents an optimistic prospect for clinical application [9, 13,14,15,16].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
