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Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery

ABSTRACT: Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery

PROVIDER: PRJNA830752 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18887200.fastq.gz	Fastqsanger.gz
	SRR18887201.fastq.gz	Fastqsanger.gz
	SRR18887202.fastq.gz	Fastqsanger.gz
	SRR18887203.fastq.gz	Fastqsanger.gz
	SRR18887204.fastq.gz	Fastqsanger.gz

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Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery

Project description:There are no curative treatment options for patients with single ventricle disease. Rather, the standard of care includes a series of palliative procedures that culminate in the Fontan operation, which, while life-saving, nevertheless reduces longevity and quality of life. The cause of late term death in these patients is typically ascribed to insidious end organ sequelae associated with the Fontan circulation. The etiology underlying these pathological processes remains unknown, but is thought to be diverse and multifactorial, arising from progressive deterioration of end-organ function due to the non-physiologic Fontan hemodynamics and its consequences on tissue perfusion and remodeling.Our overall goal is to evaluate the impact of Fontan physiology on cardiopulmonary remodeling over long periods in an ovine Fontan survival model.

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Transcriptomic Analysis of Circulating Extracellular Vesicles and Serum during the Perioperative period of Fontan and Glenn Surgery

Project description:Single-ventricle defects are palliatively corrected using the Glenn and Fontan procedures that provide lifesaving relief but lead to early mortality rates and poor prognosis post-operatively. The pathophysiology of these complications is diverse, and there are no clear predictors for these outcomes. As such, we aimed to identify novel biomarkers for single-ventricle associated outcomes through the characterization of the serum transcriptome and small extracellular vesicles (sEVs). We report on molecular responses in serum and sEVs pre-operatively and post-operatively in patients undergoing either Glenn or Fontan operations. We found that transcriptomes of serum RNA and sEV RNA are distinctly different, whereas differences between the Fontan and Glenn transcriptomes did not show any significant changes. An in vitro wound healing assay further confirmed that post-operative sEVs have higher angiogenic potential. Moreover, we used a partial-least square regression model to identify 100 RNAs and 50 microRNAs that are involved in angiogenesis-related pathways and accurately predict our wound healing results and compared them with our previously published models of ovine Fontan surgery. Lastly, an EV-origin analysis showed decreased secretion of sEV from cardiac tissue in post-operative samples and increased secretion of sEVs from stomach and nervous tissue. Overall, this study provided evidence that the circulating sEVs transcriptome are potent biomarkers and demonstrated the role of sEVs as a possible mediator for formation of veno-venous collaterals.

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Transcriptomic Analysis of Circulating Extracellular Vesicles and Serum during the Perioperative period of Fontan and Glenn Surgery

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Project description:Evaluate differences in gene methylation levels between offspring born after maternal bariatric surgery and their siblings born before surgery

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