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Severe hyperchylomicronemia sensitizes the heart to pathological remodeling: evidence from GPIHBP1 deficient mice

ABSTRACT: This dataset contains bulk RNA sequencing data generated from cardiac tissues of wild-type (WT) and Gpihbp1 knockout (Gpihbp1−/−) mice. GPIHBP1 deficiency disrupts intravascular triglyceride-rich lipoprotein hydrolysis and results in severe hyperchylomicronemia. To investigate the molecular changes associated with chronic triglyceride-rich lipoprotein accumulation in the heart, total RNA was isolated from cardiac tissues and subjected to high-throughput transcriptome sequencing. These data provide a resource for characterizing gene expression alterations and biological pathways associated with cardiac metabolic remodeling, mitochondrial dysfunction, and heart failure susceptibility in the setting of severe hypertriglyceridemia.

ORGANISM(S): Mus musculus

PROVIDER: GSE334977 | GEO | 2026/06/15

REPOSITORIES: GEO

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Project description:Abstract Aim: Circulating triglyceride and triglyceride-rich lipoprotein (TRL) accumulation is increasingly recognized as a residual atherosclerotic risk, but their specific effect in cardiac remodeling and heart failure (HF) remain largely unexplored. Here we investigated this issue in Gpihbp1 knockout (KO) mice, which develop severe hyperchylomicronemia due to disruption of intravascular TRL hydrolysis . Methods: Cardiac lipid metabolism and remodeling were evaluated in 10-month-old Gpihbp1 KO mice and wild-type littermates under physiological conditions. Mice were also subjected to transverse aortic constriction (TAC) to evaluate the impact of severe hyperchylomicronemia on pressure overload-induced remodeling and HF. Furthermore, Gpihbp1 KO mice were crossed into Ldlr KO background to study hyperchylomicronemia’s effects on hemorheology and high-fat diet (HFD)-induced cardiac pathology. Results: Untargeted cardiac lipidomics revealed 214 differentially regulated lipid species specifically enriched in glycerophospholipids, fatty acid (FA) and diacylglycerol subclasses. qPCR confirmed down-regulated FA oxidation genes and upregulated glucose utilization genes. Electron microscopy showed swollen mitochondria with fragmented cristae, and RNA-seq demonstrated reduced respiratory-chain gene expression. These derangements culminated in impaired cardiac contractile performance in 10-month-old Gpihbp1 KO mice without inducing hypertrophy or fibrosis. After TAC, Gpihbp1 KO hearts exhibited exaggerated diastolic dysfunction, increased myocyte hypertrophy, and fibrosis. In Gpihbp1/Ldlr double knockout (dKO) mice, reduced erythrocyte deformability and increased whole blood viscosity were observed and worsened post-HFD. Additionally, HFD feeding precipitated significant diastolic impairment, cardiac hypertrophy and fibrosis in dKO mice. Conclusion: Severe hyperchylomicronemia due to GPIHBP1 deficiency sensitizes the heart to pathological remodeling and HF. These findings indicate a potential pathogenic contribution of HTG and TRL accumulation to cardiac disease.

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Severe hyperchylomicronemia sensitizes the heart to pathological remodeling: evidence from GPIHBP1 deficient mice

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