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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
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Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

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Related Experiment Video

Updated: Jun 16, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
11:44

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Sexually Dimorphic Regulation of MiR-29a/c-3p in Human Endothelial Cells: Cell Functions and Transcriptome.

Si-Yan Zhang1, Colman I Freel1, Chi Zhou2

  • 1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Journal of Cellular Physiology
|June 15, 2026
PubMed
Summary

Preeclampsia's endothelial dysfunction may involve sex-specific effects of microRNAs (miRNAs) on cellular responses. Downregulating miR-29a/c-3p impairs vascular endothelial growth factor-A (VEGFA) signaling differently in male and female cells, suggesting novel therapeutic targets.

Keywords:
angiogenic factorsendothelial functionmicroRNAssexual dimorphismtranscriptome

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Published on: April 6, 2012

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Preeclampsia (PE) is a leading cause of pregnancy complications, characterized by endothelial dysfunction.
  • The precise etiology of PE is unknown, but microRNA (miRNA) dysregulation in endothelial cells is implicated.
  • Previous work showed PE downregulates miR-29a-3p and miR-29c-3p (miR-29a/c-3p), and their knockdown impairs human umbilical vein endothelial cell (HUVEC) function.

Purpose of the Study:

  • To investigate whether miR-29a/c-3p knockdown sex-specifically affects HUVEC responses to vascular endothelial growth factor-A (VEGFA) and fibroblast growth factor 2 (FGF2).
  • To explore the impact of miR-29a/c-3p knockdown on the HUVEC transcriptome and identify sex-specific gene expression changes.

Main Methods:

  • miR-29a/c-3p were inhibited in male and female HUVECs using miR-29c-3p inhibitors.
  • Cellular chemotaxis and proliferation in response to VEGFA and FGF2 were assessed.
  • RNA sequencing (RNA-seq) was performed to analyze global gene expression changes and identify regulated pathways.

Main Results:

  • miR-29c-3p inhibitors significantly reduced miR-29a/c-3p levels in both male and female HUVECs.
  • VEGFA-stimulated chemotaxis was suppressed by miR-29c-3p inhibitors in male HUVECs (26%), but not in female HUVECs.
  • RNA-seq revealed distinct transcriptomic alterations, with 47 genes dysregulated in male and 118 in female HUVECs, associated with sex-specific pathways.

Conclusions:

  • miR-29a/c-3p knockdown sex-specifically impacts HUVEC responses to VEGFA, suggesting a role in PE-related endothelial dysfunction.
  • Transcriptomic analysis highlights sex-specific gene expression changes regulated by miR-29a/c-3p.
  • Dysregulated genes present potential sex-specific therapeutic targets for preeclampsia.