Upregulation of MMP-9 and CaMKII prompts cardiac electrophysiological changes that predispose denervated transplanted hearts to arrhythmogenesis after prolonged cold ischemic storage

Li, WeiChao; Gao, Hong; Gao, Ju; Wang, Zijun

doi:10.1016/j.biopha.2019.108641

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…CaMKII serves an important regulatory role in the mechanism of VA. Overexpression of CaMKII can promote the occurrence of DADs and EADs by increasing the extent of I Na,L , decreasing the intensity of I to , I K1 and I K , and increasing Ca 2+ in the cytoplasm, thereby inducing VA. Additionally, CaMKII activation is closely related to connexin 43 dysregulation; however, CaMKII activation also indirectly decreases the expression and subcellular localization of connexin 43 in intercalated discs. Both effects potentially increase arrhythmogenic susceptibility (49)(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of calcium/calmodulin‑dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review)

Guo

et al. 2021

Exp Ther Med

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Ventricular arrhythmia (VA) is a highly fatal arrhythmia that involves multiple ion channels. Of all sudden cardiac death events, ~85% result from VAs, including ventricular tachycardia and ventricular fibrillation. Calcium/calmodulin-dependent pro-tein kinase II (CaMKII) is an important ion channel regulator that participates in the excitation-contraction coupling of the heart, and as such is important for regulating its electrophysiological function. CaMKII can be activated in a Ca 2+ /calmodulin (CaM)-dependent or Ca 2+ /CaM-independent manner, serving a key role in the occurrence and development of VA. The present review aimed to determine whether activated CaMKII induces early afterdepolarizations and delayed afterdepolarizations that result in VA by regulating sodium, potassium and calcium ions. Assessing VA mechanisms based on the CaMKII pathway is of great significance to the clinical treatment of VA and the de-velopment of effective drugs for use in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of calcium/calmodulin‑dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review)

Guo

et al. 2021

Exp Ther Med

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“…The ECG was amplified and analyzed using a BL-420 biological function system. Bipolar electrograms between the atrial and ventricular electrodes were used to monitor arrhythmias [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

Tang

Gao

et al. 2020

J Cardiothorac Surg

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Background Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored. Methods Sprague-Dawley (SD) rats were randomly divided into two groups ( n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR). Results Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17. Conclusions Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.

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Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts

Hu,

Duan,

Gao

et al. 2024

Cytotechnology

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Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immuno uorescence and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemiareperfusion.

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Upregulation of MMP-9 and CaMKII prompts cardiac electrophysiological changes that predispose denervated transplanted hearts to arrhythmogenesis after prolonged cold ischemic storage

Cited by 7 publications

References 33 publications

Regulatory mechanism of calcium/calmodulin‑dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review)

Regulatory mechanism of calcium/calmodulin‑dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review)

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts

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