Transcriptome analysis in heart failure

Matkovich, Scot J.

doi:10.1097/hco.0000000000000275

Cited by 11 publications

(6 citation statements)

References 68 publications

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“…In the past two decades, global transcriptome analysis by microarray or RNA-seq has been greatly applied not only to explore the molecular mechanism underlying the pathogenesis of ischemic heart diseases but also to identify biomarkers useful for diagnostic, prognostic, and therapeutic purposes. Numerous genes have been recognized as causative or responsive factors in the repair and remodeling of the infarcted heart [32][33][34]. However, few studies have revealed their temporal changes after MI [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Wang

Xiao

Zhang

et al. 2022

BMC Cardiovasc Disord

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Background Hypoxia inducible factor-1 (HIF-1) plays a key role in modulating post-infarct healing after myocardial ischemic injury through transcriptional regulation of hundreds of genes involved in diverse cardiac remodeling processes. However, the dynamic changes in HIF-1 target gene expression in the ischemic heart after myocardial infarction (MI) have not been well characterized. Methods We employed a rhesus monkey model of MI induced by left anterior descending artery ligation and examined the expression pattern of HIF-1 target genes in the ischemic heart at 1, 7, and 28 days after injury by bulk RNA-sequencing analysis. Results Myocardial transcriptomic analysis demonstrated a temporal-specific regulation of genes associated with the inflammatory response, cell proliferation, fibrosis and mitochondrial metabolism during the pathological progression of MI. HIF-1 target genes involved in processes related to glycolysis, angiogenesis, and extracellular matrix (ECM) remodeling also exhibited distinct expression patterns during MI progression. Copper concentrations were gradually decreased in the heart after ischemic injury, which was positively correlated with the expression of HIF-1-mediated angiogenic and glycolytic genes but negatively correlated with the expression of HIF-1-mediated ECM remodeling genes. Moreover, genes related to intracellular copper trafficking and storage were suppressed along with the loss of myocardial copper in the ischemic heart. Conclusions This study demonstrated a dynamic, functional-specific regulation of HIF-1 target gene expression during the progression of MI. The fine-tuning of HIF-1 signaling in the ischemic heart may be relate to the alteration in myocardial copper homeostasis. These findings provide transcriptomic insights into the distinct roles of HIF-1 signaling in the heart after ischemic injury, which will help determine the beneficial cutoff point for HIF-1 targeted therapy in ischemic heart diseases.

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Section: Discussionmentioning

confidence: 99%

Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Wang

Xiao

Zhang

et al. 2022

BMC Cardiovasc Disord

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“…However, the predictive value of the RNA signature requires elucidation in large clinical trials. 62 However, metabolomic and lipidomic phenotyping of patients having HFrEF/HFpEF to indicate a profile of oxidative stress, lactic acidosis, and metabolic syndrome, coupled with mitochondria dysfunction, is a promising approach to stratify them at high risk of poor outcomes. 63…”

Section: Prospectivesmentioning

confidence: 99%

Biomarker-Based Guideline-Directed Medical Therapy of Heart Failure: The Gap Between Guidelines and Clinical Practice

Berezin¹,

Berezin²

2021

EMJ Cardiol

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Current clinical recommendations provided by the 2016 European Society of Cardiology (ESC) and 2017 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) are substantially distinguished in the use of circulating biomarkers in the management of heart failure (HF). To date, natriuretic peptides continue being the universal biomarkers used in diagnosis, risk stratification, and prediction of cardiovascular death, all-cause mortality, and HF-related outcomes for patients with both phenotypes of HF. However, biomarkers of fibrosis and inflammation, including soluble suppressor of tumourgenicity 2 and galectin-3, were able to increase predictive ability of natriuretic peptides in HF patients regardless of cardiovascular risk-factor presentation and HF phenotypes. Therefore, there are many various biomarkers describing several pathophysiological processes such as fibrosis, inflammation, oxidative stress, neurohumoral activation, extracellular matrix turnover, and vascular reparation, that play a pivotal role in the natural evolution of HF. This review discusses whether multiple biomarker models are more effective than a single biomarker in improving risk stratification strategies in patients with HF. It emphasises how in routine clinical practice, the multiple biomarker approach to elicit response to therapy of HF and predict clinical outcomes is rare, probably because of the relatively high cost, low affordability, lack of clear recommendations for clinical implementation, and significant disagreements in the interpretation of the data obtained.

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“…Transcriptome analysis in large animal model of HF is widely used in HF research ( 6 , 7 ). In recent years, transcript data in HF model have been analyzed by the next-generation sequencing (NGS) or Affymetrix exon arrays (Santa Clara, CA, USA), such as prediction of alternative splicing (AS) events and lncRNAs ( 8 , 9 ). However, these techniques had limitations in recognizing AS isoforms, homologous gene families, and complete and accurate assembly of transcripts because of short read data.…”

Section: Introductionmentioning

confidence: 99%

Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure

Liang

Bai

Wang

et al. 2021

Front. Cardiovasc. Med.

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Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.

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Transcriptome analysis in heart failure

Cited by 11 publications

References 68 publications

Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury

Biomarker-Based Guideline-Directed Medical Therapy of Heart Failure: The Gap Between Guidelines and Clinical Practice

Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure

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