Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure

Zhang, Yunhe; Chen, Ao; Song, Lei; Li, Min; Luo, Zhangyuan; Zhang, Wenzan; Chen, Yingmin; He, Ben

doi:10.1536/ihj.15-516

Cited by 15 publications

(12 citation statements)

References 45 publications

(42 reference statements)

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“…[1][2][3] Ryanodine receptor (RyR) is one family of intracellular Ca 2+ release channels which regulates the release of Ca 2+ from the endoplasmic reticulum or sarcoplasmic reticulum into the cytosol. 4) RyR is the largest known ion channel, in form of homotetramers (approximately 2,200 kDa), each subunit of which is comprised of a large N-terminal cytoplasmic domain, accounting for 4/5 of the protein, that modulates the gating of the channel, and 1/5 proportion being luminal and transmembrane spanning (TM) domains.…”

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confidence: 99%

Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

et al. 2017

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SummaryRyanodine receptors (RyRs), the large homotetrameric protein complexes, regulate the release of calcium from intracellular stores into the cytosol and play vital roles in the excitation-contraction coupling of cells. However, the evolutionary relationship of RyRs in vertebrates has yet to be elucidated. We identified 22 RyRs from Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Anolis carolinensis, Rana catesbeiana, and Danio rerio. The phylogenetic relationship, motifs analysis and reconstruction of ancestral RyRs showed that the members of RyR family in vertebrates were grouped into three clades: the RyR1 clade, the RyR2 clade, and the RyR3 clade. Positive selection existed in RyR gene evolution, which is consistent in three site models, and gene ontology (GO) analysis showed that the evolution of RyR family in vertebrates promotes RyRs function differentiation. At last, we predicted 140 mutation sites which may be involved in diseases and 57 phosphorylation sites among RyR1 sequence in human, as well as 61 mutation sites and 70 phosphorylation sites in human RyR2 sequences. Most of these potential sites are arranged in clusters. Our work provides insight into the origin and evolutionary process of RyRs in vertebrates, facilitating their functional investigations in the future.(Int Heart J 2017; 58: 969-977)

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confidence: 99%

Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

et al. 2017

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“…Experimental preservation of vagal activity after myocardial ischaemia maintains normal calcium handling by restoring the protein and mRNA levels of sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a), NCX1 and phospholamban. 41 The main strength of our study was investigating two separate populations in which we could obtain samples using optimised protocols that enabled microRNA detection in serum and plasma extracellular vesicles to address our overarching hypothesis. Moreover, we compared serial changes in microRNA masked to troponin levels before and after surgery.…”

Section: Discussionmentioning

confidence: 99%

microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study

May

Abbott

Arroyo

et al. 2020

Preprint

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Background: Elevated plasma/serum troponin, indicating perioperative myocardial injury (PMI), is common after non-cardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. Methods: Nested case-control study of samples obtained before and after non-cardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with/without PMI, matched for age, gender and comorbidity. Real-time polymerase chain reaction quantified relative microRNA expression (cycle quantification threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). Results: MicroRNA were detectable in all 59 patients (median age:67yrs (61-75); 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, PMI was not associated with increased serum microRNA expression levels after surgery (hsa-miR-1-3p mean fold-change (FC): 3.99 (95%CI:1.95-8.19); hsa-miR-133-3p FC:5.67(95%CI:2.94-10.91); p<0.001). hsa-miR-208b-3p was more commonly detected after PMI (odd ratio (OR):10.0 (95%CI:1.9-52.6); p<0.01). Bioinformatic analysis of differentially expressed microRNAs from cohorts one and two identified pathways associated with adrenergic stress involving calcium dysregulation, rather than ischaemia. Conclusions: Circulating microRNAs synonymous with cardiac ischaemia were universally elevated in patients after surgery, independent of developing myocardial injury.

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“…Although animal studies of drugs targeting NPY and galanin receptors are promising, clinical translation of experimental data is challenging. Vagal nerve stimulation and carotid baroreflex activation therapies are examples of device therapies with disappointing results ( 24 , 25 ). The failure of recent clinical trials proved that the autonomic nervous system is not an easy target.…”

Section: Discussionmentioning

confidence: 99%

Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander?

Gür

Sağbaş²,

Akyüz³

et al. 2017

Anatol J Cardiol

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Objective:Galanin, a cotransmitter similar to neuropeptide Y (NPY), aggravates autonomic imbalance in systolic heart failure (HF) by attenuating vagal tonus after burst sympathetic activity. In animal HF models, galanin antagonists have improved cardiac function. To determine whether galanin is a promising therapeutic target in HF, we studied its concentrations in HF patients and evaluated its correlation with NPY, markers of humoral activity such as pro-BNP and copeptin, and echocardiographic parameters of HF severity.Methods:After recording demographic and echocardiographic characteristics of 87 individuals (57 HF patients and 30 control subjects), fasting serum concentrations of galanin, NPY, copeptin, and pro-BNP were determined.Results:Unlike pro-BNP, copeptin, and NPY, which were significantly elevated in HF patients (p<0.001, p<0.001, and p=0.001, respectively), galanin was similar in HF patients and control subjects (p=0.9). NPY correlated with the echocardiographic parameters of HF severity (r=–0.22, p=0.03 for EF; r=0.3, p=0.005 for Tei index of RV; r=–0.23, p=0.03 for TAPSE; and r=0.24, p=0.024 for E/e¢) and pro-BNP (r=0.22, p=0.046). NPY levels were also associated with beta blocker (BB) use, wherein BB significantly decreased NPY in both HF patients and control subjects. Galanin correlated with humoral biomarkers, pro-BNP and copeptin (r=0.39, p<0.001 and r=0.41, p<0.001, respectively). Although current smoking, BB therapy, pro-BNP, copeptin, and body mass index were associated with galanin in univariate analyses, the multiple linear regression model revealed that pro-BNP was the only significant determinant of galanin levels in HF patients.Conclusion:Our findings confirmed the role of NPY in autonomic balance and suggest that galanin is associated with the proadrenergic state, but its role in HF in humans remains unclear.

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Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure

Cited by 15 publications

References 45 publications

Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study

Role of sympathetic cotransmitter galanin on autonomic balance in heart failure: an active player or a bystander?

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