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Updated: Jan 3, 2026

In Vitro Model of Coronary Angiogenesis
Published on: March 10, 2020
Genetic variants of VEGFR-1 gene promoter in acute myocardial infarction
Haihua Wang1, Shufang Zhang2, Na Wang3
1Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, China.
Insights
Genetic variants in the Vascular Epithelial Growth Factor Receptor-1 (VEGFR-1) gene promoter were identified in patients with Acute Myocardial Infarction (AMI). These variants may impact VEGFR-1 gene activity, potentially contributing to AMI development.
Area of Science:
- Cardiovascular Genetics
- Molecular Biology
- Disease Pathogenesis
Background:
- Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a complex condition driven by atherosclerosis.
- Vascular Epithelial Growth Factor Receptor-1 (VEGFR-1) plays a role in angiogenesis and vascular permeability, and its absence leads to cardiac issues in mice.
- VEGFR-1 gene variants are hypothesized to be involved in CAD due to observed cardiac dysfunction and fibrosis in related studies.
Purpose of the Study:
- To investigate the potential role of VEGFR-1 gene variants in the development of AMI.
- To genetically and functionally analyze the VEGFR-1 gene promoter in large cohorts of AMI patients and controls.
Main Methods:
- Identification of DNA sequence variants (DSVs) and single-nucleotide polymorphisms (SNPs) in the VEGFR-1 gene promoter and 5'-untranslated region.
- Functional analysis of identified variants using reporter gene assays in HEK-293 and H9c2 cells to assess transcriptional activity.
- Electrophoretic mobility shift assays (EMSA) to evaluate the impact of variants on transcription factor binding.
Main Results:
- Sixteen DNA sequence variants (DSVs), including six single-nucleotide polymorphisms (SNPs), were identified in the VEGFR-1 gene promoter and 5'-untranslated region.
- Five novel DSVs and one SNP were exclusively found in the AMI patient group.
- These variants significantly altered VEGFR-1 gene promoter transcriptional activity and affected transcription factor binding.
Conclusions:
- Genetic variants within the VEGFR-1 gene promoter identified in AMI patients may influence its transcriptional activity.
- These alterations in transcriptional activity could lead to changes in VEGFR-1 levels, potentially contributing to the pathogenesis of AMI.
Background:
Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. Vascular epithelial growth factor receptor-1 (VEGFR-1) stimulates angiogenesis and vascular permeability, and functions as a decoy to sequester VEGF and prevent initiation of intracellular signaling. VEGFR-1 knockout mice exhibit significantly higher mortality due to heart failure, cardiac hypertrophy, and cardiac dysfunction. An evident increase in macrophage infiltration and cardiac fibrosis are also observed after transverse aortic constriction. Therefore, VEGFR-1 gene variants may be involved in CAD. In this study, VEGFR-1 gene promoter was genetically and functionally analyzed in large cohorts of AMI patients and ethnic-matched controls.
Results:
A total of 16 DNA sequence variants (DSVs) including six single-nucleotide polymorphisms (SNPs) were found in the VEGFR-1 gene promoter and 5'-untranslated region. Five novel DSVs and one SNP were only identified in AMI patients group. These DSVs and SNP significantly altered the transcriptional activity of the VEGFR-1 gene promoter in both HEK-293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay indicated that the DSVs and SNPs evidently affected the binding of transcription factors.
Conclusions:
The genetic variants in VEGFR-1 gene identified in AMI patients may alter the transcriptional activity of the VEGFR-1 gene promoter and change VEGFR-1 level, contributing to AMI development.
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