Related Experiment Video

Updated: Jun 26, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Dominant-negative loss of PPARgamma function enhances smooth muscle cell proliferation, migration, and vascular

Dane Meredith1, Manikandan Panchatcharam, Sumitra Miriyala

  • 1Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|January 31, 2009
PubMed
Abstract

Insights

Peroxisome proliferator activated receptor-gamma (PPARgamma) normally inhibits smooth muscle cell migration and proliferation. Disrupting PPARgamma signaling in mice accelerated atherosclerosis development and intimal hyperplasia after arterial injury.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Diabetes Research

Background:

  • Peroxisome proliferator activated receptor-gamma (PPARgamma) is a nuclear receptor targeted by thiazolidinediones (TZDs) for diabetes treatment.
  • PPARgamma agonists are thought to slow atherosclerosis, but some TZDs may increase cardiovascular risk.
  • The role of PPARgamma in smooth muscle cell (SMC) function related to atherosclerosis requires further investigation.

Purpose of the Study:

  • To investigate the role of PPARgamma signaling in SMC proliferation and migration.
  • To determine the in vivo consequences of disrupted PPARgamma signaling on atherosclerosis development.

Main Methods:

  • Genetic disruption of PPARgamma signaling using a dominant-negative mutation (P465L) in mice.
  • In vitro analysis of SMC proliferation and migration from PPARgamma(L/+) mice.
  • Assessment of intimal hyperplasia in PPARgamma(L/+) mice after arterial injury.

Main Results:

  • PPARgamma(L/+) SMCs showed increased proliferation and migration compared to wild-type cells.
  • Upregulation of ETS-1 correlated with enhanced SMC proliferation and migration.
  • PPARgamma(L/+) mice exhibited a 4.3-fold increase in intimal hyperplasia following arterial injury.

Conclusions:

  • PPARgamma plays a normal inhibitory role in SMC migration and proliferation.
  • These findings suggest PPARgamma signaling is protective against atherosclerosis and restenosis.

More Related Videos

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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...