Exploring Potential Causality and Molecular Mechanisms between Heart Failure and Renal Failure: Insights from Mendelian Randomization Studies, the MIMIC-IV Database and the Gene Expression Omnibus Database.

IF 2.3 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE
Shaoyi Peng, Hailong Li, Kaiyuan Li
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引用次数: 0

Abstract

Introduction: Heart failure (HF) and renal failure (RF) frequently coexist as cardiorenal syndrome, but their underlying causal mechanisms remain poorly defined.

Methods: This study applied Mendelian randomization (MR) using genome-wide association study (GWAS) datasets to investigate the causal effect of HF on RF. The inverse variance weighted method assessed causality, and summary-data-based MR (SMR) was used to identify therapeutic targets. Additional analyses included 211 gut microbiota traits and 1,400 serum metabolites. Validation was performed using the MIMIC-IV database. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and key transcription factors (TFs).

Results: This study found that HF significantly increases the risk of RF (OR = 1.54, 95% CI: 1.07-2.23, p = 0.020). SMR analysis identified SURF1 and MAP3K11 as potential therapeutic targets for HF and RF. One gut microbiota genus and one serum metabolite showed causal associations with both diseases. MIMIC-IV data supported the HF-RF association (OR = 2.94, 95% CI: 2.81-3.07, p < 0.001). A total of 11 overlapping DEGs were enriched in the MAPK cascade, with RELA identified as a key TF.

Conclusion: This study provides genetic and molecular evidence supporting a causal role of HF in RF, highlighting microbial, metabolic, and immune mechanisms as potential therapeutic targets.

探索心力衰竭和肾衰竭之间的潜在因果关系和分子机制:来自孟德尔随机化研究、MIMIC-IV数据库和GEO数据库的见解
背景:心衰(HF)和肾功能衰竭(RF)经常作为心肾综合征共存,但其潜在的因果机制尚未明确。方法:本研究采用孟德尔随机化(MR)方法,使用全基因组关联研究(GWAS)数据集来研究HF对RF的因果关系。反方差加权(IVW)方法评估因果关系,基于汇总数据的MR (SMR)用于确定治疗靶点。额外的分析包括211个肠道微生物群特征和1400个血清代谢物。使用MIMIC-IV数据库进行验证。分析转录组学数据以鉴定差异表达基因(DEGs)和关键转录因子。结果:本研究发现HF显著增加RF的风险(OR = 1.54, 95% CI: 1.07-2.23, P = 0.020)。SMR分析发现SURF1和MAP3K11是HF和RF的潜在治疗靶点。一种肠道菌群属和一种血清代谢物显示出与两种疾病的因果关系。MIMIC-IV数据支持HF-RF相关性(OR = 2.94, 95% CI: 2.81-3.07, P < 0.001)。在MAPK级联中富集了11个重叠的deg,其中RELA被确定为关键转录因子。结论:本研究提供了遗传和分子证据,支持HF在RF中的因果作用,强调微生物、代谢和免疫机制是潜在的治疗靶点。
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来源期刊
Journal of Vascular Research
Journal of Vascular Research 医学-生理学
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
>12 weeks
期刊介绍: The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.
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