Related Experiment Video

Updated: Jul 19, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis

Laura Piqueras1, Andrew R Reynolds, Kairbaan M Hodivala-Dilke

  • 1Cardiac, Vascular & Inflammation Research, William Harvey Research Institute, Barts and the London, Queen Mary University London, Charterhouse Sq, London EC1M 6BQ, UK.

Arteriosclerosis, Thrombosis, and Vascular Biology
|October 28, 2006
PubMed
Abstract

Insights

Peroxisome-proliferator activated receptor (PPAR)-beta/delta activation promotes endothelial cell proliferation and angiogenesis. This pathway, involving vascular endothelial growth factor (VEGF), highlights potential risks for GW501516 in dyslipidemia patients prone to angiogenic disorders.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • The function of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-beta/delta in endothelial cells is not well understood.
  • The selective PPARbeta/delta ligand GW501516 is currently undergoing clinical trials for dyslipidemia treatment.

Purpose of the Study:

  • To investigate the role of PPARbeta/delta in endothelial cell proliferation and angiogenesis using the selective ligand GW501516.
  • To determine the molecular mechanisms underlying PPARbeta/delta-mediated effects on endothelial cells.

Main Methods:

  • Western blot analysis to confirm PPARbeta/delta expression in human and murine endothelial cells.
  • In vitro assays measuring endothelial cell proliferation, morphogenesis, and outgrowth.
  • In vivo matrigel plug assay to assess angiogenesis.
  • Analysis of vascular endothelial cell growth factor (VEGF) and adipose differentiation-related protein (ADRP) expression.
  • Experiments using dominant-negative PPARbeta/delta and VEGF receptor antagonists.

Main Results:

  • PPARbeta/delta was expressed in various endothelial cell types.
  • GW501516 significantly enhanced endothelial cell proliferation, morphogenesis, and in vivo angiogenesis.
  • GW501516 upregulated VEGF and ADRP expression.
  • Inhibition of PPARbeta/delta or VEGF signaling abolished GW501516-induced effects.
  • GW501516 treatment increased endothelial cell outgrowth and tube formation.

Conclusions:

  • PPARbeta/delta acts as a novel regulator of endothelial cell proliferation and angiogenesis, primarily mediated through VEGF.
  • The therapeutic use of GW501516 for dyslipidemia warrants caution in patients at risk for angiogenic disorders due to its pro-angiogenic effects.

More Related Videos

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis05:30

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis

Published on: November 8, 2024

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...