Transcriptome Discovery of Genes in the Three Phases of Autophagy That Are Upregulated During Atrial Fibrillation

Kamihara, Takahiro; Hirashiki, Akihiro; Kokubo, Manabu; Shimizu, Atsuya

doi:10.1253/circrep.cr-22-0130

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…Life phenomena, such as autophagy, which is involved in aging [9][10][11], are also involved in AF onset. Using bioinformatic analysis, we also showed that autophagy was increased in the left atrium of patients with AF [12].…”

Section: Introductionmentioning

confidence: 82%

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Kamihara,

Kinoshita,

Kawano

et al. 2024

Cardiology

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Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. Methods: Gene expression data was analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p-value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used RefEx to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. Results: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, Reference expression (RefEx) was used to analyze the gene expression levels in various tissues. Four genes; FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. Conclusion: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.

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Section: Introductionmentioning

confidence: 82%

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Kamihara,

Kinoshita,

Kawano

et al. 2024

Cardiology

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“… 20 Even in case of atrial fibrillation, our previous research revealed that atrial fibrillation is related to autophagy. 21 It was also elucidated that the frequency of occurrence of “mitophagy” increased significantly since 2019. When we compared the word clouds created for “1984–2018” and “2019–2023” (Figure 3A,B ), the term “mitochondria” appeared frequently until 2008, and the term “autophagy” appeared frequently since 2018.…”

Section: Discussionmentioning

confidence: 99%

Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging

Kamihara,

Tanaka,

Omura

et al. 2024

Aging Medicine

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ObjectivesWe conducted a text mining analysis of 40 years of literature on cardiac aging from PubMed to investigate the current understanding on cardiac aging and its mechanisms. This study aimed to embody what most researchers consider cardiac aging to be.MethodsWe used multiple text mining and machine learning tools to extract important information from a large amount of text.ResultsAnalysis revealed that the terms most frequently associated with cardiac aging include “diastolic,” “hypertrophy,” “fibrosis,” “apoptosis,” “mitochondrial,” “oxidative,” and “autophagy.” These terms suggest that cardiac aging is characterized by mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. We also revealed an increase in the frequency of occurrence of “autophagy” in recent years, suggesting that research on autophagy has made a breakthrough in the field of cardiac aging. Additionally, the frequency of occurrence of “mitophagy” has increased significantly since 2019, suggesting that mitophagy is an important factor in cardiac aging.ConclusionsCardiac aging is a complex process that involves mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. Further research is warranted to elucidate the mechanisms of cardiac aging and develop strategies to mitigate its detrimental effects.

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“…For intergroup comparison, rank products were utilized after normalizing the intensity files. Expression change was selected when the false discovery rate (FDR) values were <0.2 [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

The Epigenetic Legacy of Maternal Protein Restriction: Renal Ptger1 DNA Methylation Changes in Hypertensive Rat Offspring

Jia,

Miyoshi,

et al. 2023

Nutrients

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Nutrient imbalances during gestation are a risk factor for hypertension in offspring. Although the effects of prenatal nutritional deficiency on the development of hypertension and cardiovascular diseases in adulthood have been extensively documented, its underlying mechanisms remain poorly understood. In this study, we aimed to elucidate the precise role and functional significance of epigenetic modifications in the pathogenesis of hypertension. To this end, we integrated methylome and transcriptome data to identify potential salt-sensitive hypertension genes using the kidneys of stroke-prone spontaneously hypertensive rat (SHRSP) pups exposed to a low-protein diet throughout their fetal life. Maternal protein restriction during gestation led to a positive correlation between DNA hypermethylation of the renal prostaglandin E receptor 1 (Ptger1) CpG island and high mRNA expression of Ptger1 in offspring, which is consistently conserved. Furthermore, post-weaning low-protein or high-protein diets modified the Ptger1 DNA hypermethylation caused by fetal malnutrition. Here, we show that this epigenetic variation in Ptger1 is linked to disease susceptibility established during fetal stages and could be reprogrammed by manipulating the postnatal diet. Thus, our findings clarify the developmental origins connecting the maternal nutritional environment and potential epigenetic biomarkers for offspring hypertension. These findings shed light on hypertension prevention and prospective therapeutic strategies.

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Transcriptome Discovery of Genes in the Three Phases of Autophagy That Are Upregulated During Atrial Fibrillation

Cited by 3 publications

References 46 publications

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging

The Epigenetic Legacy of Maternal Protein Restriction: Renal Ptger1 DNA Methylation Changes in Hypertensive Rat Offspring

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