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<p>The objective of this study is to identify T2DM-associated biomarkers linked to diabetic cardiac dysfunction-related transcriptomic signatures through integrated transcriptomic and Mendelian randomization analysis and evaluate cynaropicrin as a candidate cardiometabolic intervention. Transcriptomic datasets from the GEO database related to diabetic cardiac dysfunction, heart failure, and cardiomyopathy-associated phenotypes were processed for differential expression analysis and WGCNA, with consideration of disease-definition and tissue-source heterogeneity. A two-sample Mendelian randomization analysis was used to evaluate genetically predicted associations between candidate gene expression and T2DM risk. External validation assessed diagnostic performance via ROC analysis. Multi-database screening and molecular docking identified candidate compounds. Streptozotocin-induced diabetic rats were treated with cynaropicrin for 8&#xa0;weeks, with comprehensive cardiac and metabolic assessment. Analysis identified 30 candidate genes with functional enrichment in proteostasis and metabolism. Mendelian randomization prioritized three T2DM-associated genetically supported genes: PPIP5K2, RBM23, and IGF2BP2. Cynaropicrin significantly improved cardiac function, reduced fibrosis, and enhanced glycemic control in diabetic rats while suppressing pro-fibrotic signaling. PPIP5K2, RBM23, and IGF2BP2 represent T2DM-associated genetically supported biomarkers dysregulated in diabetic cardiac dysfunction-related datasets with diagnostic potential. Cynaropicrin demonstrates candidate cardioprotective and metabolic benefits in diabetic rats; however, its direct molecular targets and mechanism of action require further validation.</p>

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Integrated transcriptomic and Mendelian randomization analysis identifies novel biomarkers for type 2 diabetes–associated cardiac dysfunction: cynaropicrin as a candidate intervention

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Lindong Zhang,
  • Lingling Qin,
  • Lili Wu,
  • Tonghua Liu

摘要

The objective of this study is to identify T2DM-associated biomarkers linked to diabetic cardiac dysfunction-related transcriptomic signatures through integrated transcriptomic and Mendelian randomization analysis and evaluate cynaropicrin as a candidate cardiometabolic intervention. Transcriptomic datasets from the GEO database related to diabetic cardiac dysfunction, heart failure, and cardiomyopathy-associated phenotypes were processed for differential expression analysis and WGCNA, with consideration of disease-definition and tissue-source heterogeneity. A two-sample Mendelian randomization analysis was used to evaluate genetically predicted associations between candidate gene expression and T2DM risk. External validation assessed diagnostic performance via ROC analysis. Multi-database screening and molecular docking identified candidate compounds. Streptozotocin-induced diabetic rats were treated with cynaropicrin for 8 weeks, with comprehensive cardiac and metabolic assessment. Analysis identified 30 candidate genes with functional enrichment in proteostasis and metabolism. Mendelian randomization prioritized three T2DM-associated genetically supported genes: PPIP5K2, RBM23, and IGF2BP2. Cynaropicrin significantly improved cardiac function, reduced fibrosis, and enhanced glycemic control in diabetic rats while suppressing pro-fibrotic signaling. PPIP5K2, RBM23, and IGF2BP2 represent T2DM-associated genetically supported biomarkers dysregulated in diabetic cardiac dysfunction-related datasets with diagnostic potential. Cynaropicrin demonstrates candidate cardioprotective and metabolic benefits in diabetic rats; however, its direct molecular targets and mechanism of action require further validation.