Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction

Kurotsu, Shota; Osakabe, Rina; Isomi, Mari; Tamura, Fumiya; Sadahiro, Taketaro; Muraoka, Naoto; Kojima, Hiroko; Haginiwa, Sho; Tani, Hideaki; Nara, Kaori; Kubota, Yoshiaki; Ema, Masatsugu; Fukuda, Keiichi; Suzuki, Takeshi; Ieda, Masaki

doi:10.1016/j.bbrc.2017.11.094

Cited by 16 publications

(17 citation statements)

References 17 publications

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“…Our results showed that both VEGFR1 and VEGFR2 were almost exclusively expressed in cardiac ECs, whereas very little, if any, expression was detected in CMCs and cardiac fibroblasts. A recent study using VEGFR1 (Flt1) and VEGFR2 (Flk1) reporter mice demonstrated that VEGFR1 is homogenously expressed in ECs throughout the heart, whereas VEGFR2 showed an epicardial-to-endocardial gradient and was downregulated in quiescent large coronary vessels in adult mice, 41 as also indicated by our previous findings. 10 Using the VEGFR2-blocking antibody DC101, we showed here that the cardiac hypertrophy induced by VEGF-B or PlGF can be prevented and, importantly, reversed by this inhibition of VEGFR2 signaling.…”

Section: Discussionsupporting

confidence: 84%

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling

et al. 2019

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Section: Discussionsupporting

confidence: 84%

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling

et al. 2019

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“…Among the remaining lncRNAs in Module 2, CARMN is associated with a super enhancer and has been shown to control cardiac specification and differentiation [ 22 ] and AC005550.2 is antisense and overlapping to Homeobox protein MOX-2 MEOX2 (also in Module 2 which regulates cardiac energy metabolism via fatty acid uptake in heart capillary endothelium [ 23 ]. Certain protein-coding genes within the module have already been associated with cardiac angiogenesis and vasculogenesis, such as Fms-Related Receptor Tyrosine Kinase 1 (FLT1) [ 24 ]. A recent paper [ 25 ] proposed that coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart

Ward

Schmeier

Saddic

et al. 2021

IJMS

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Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted p < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = −0.69, p = 1 × 10−23) and activation of cell death pathways (p < 6 × 10−9). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient −0.2, p = 0.002). Conclusion: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.

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“…Ado downregulates sVEGFR-1 and upregulates VEGFR-1 production to stimulate angiogenesis in the heart [33]. Mouse studies have shown that after myocardial infarction, expression of VEGFR-1 is induced in the regenerating coronary vessels at day 7 and is maintained in the newly formed coronary vessels until 30 days after myocardial infarction, recapitulating their expression kinetics during development [10].…”

Section: Discussionmentioning

confidence: 99%

“…VEGFR-1 binds to vascular endothelial growth factor A (VEGF-A) and placental growth factor (PLGF) to stimulate angiogenesis and vascular permeability [9]. VEGFR-1 gene is homogeneously expressed in vascular epithelial cells of neonatal mouse hearts, and in coronary vessels of adult hearts [10]. sFlt-1 levels are dramatically stimulated in most cases of hypoxia [11].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants of VEGFR-1 gene promoter in acute myocardial infarction

et al. 2019

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BackgroundCoronary 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.ResultsA 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.ConclusionsThe 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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Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction

Cited by 16 publications

References 17 publications

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling

Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart

Genetic variants of VEGFR-1 gene promoter in acute myocardial infarction

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