Related Experiment Video

Updated: May 13, 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 PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in

Christopher J Pelham1, Henry L Keen, Steven R Lentz

  • 1Departments of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|March 1, 2013
PubMed

Insights

Dominant-negative PPARγ in blood vessels worsens atherosclerosis and hypertension in mice. This suggests blocking PPARγ in the endothelium or smooth muscle may drive cardiovascular disease.

Area of Science:

  • Cardiovascular Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Nuclear hormone receptor agonists, peroxisome proliferator-activated receptor γ (PPARγ), improve insulin sensitivity and slow atherosclerosis in Type II diabetes.
  • Dominant-negative (DN) PPARγ mutations cause hypertension and Type II diabetes, suggesting a critical role for functional PPARγ in vascular health.

Purpose of the Study:

  • To investigate if DN PPARγ in vascular endothelium and smooth muscle exacerbates atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice.
  • To determine the impact of DN PPARγ on vascular function, blood pressure, and atherogenic marker expression.

Main Methods:

  • Generated ApoE(-/-) mice with endothelium-specific or smooth muscle-specific expression of DN PPARγ.
  • Assessed vascular function via aortic ring relaxation assays.
  • Measured systolic blood pressure.
  • Analyzed the expression of atherogenic markers (e.g., Cd36, Mcp1, Osteopontin, Vcam1, Catalase) and atherosclerotic lesion formation in the aorta.

Main Results:

  • Endothelium-specific DN PPARγ impaired endothelium-dependent relaxation, increased systolic blood pressure, altered atherogenic marker expression, and enhanced diet-induced atherosclerosis.
  • Smooth muscle-specific DN PPARγ also increased systolic blood pressure and aortic dysfunction, leading to enhanced atherosclerosis.
  • Smooth muscle-specific DN PPARγ altered distinct atherogenic markers, including Osteopontin, correlating with increased plaque calcification.

Conclusions:

  • Inhibition of PPARγ function in the vascular endothelium or smooth muscle exacerbates atherosclerosis.
  • DN PPARγ-mediated interference with wild-type PPARγ in these vascular cells contributes to cardiovascular disease development.
  • Targeting PPARγ in specific vascular cells may offer therapeutic strategies for atherosclerosis and related cardiovascular complications.
Keywords:
PPARγatherosclerosisendotheliumsmooth muscle

Related Concept Videos

Peripheral Artery Disease I: Introduction01:30

Peripheral Artery Disease I: Introduction

Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs, particularly the arteries supplying the thighs and calves. In rare cases, it may involve other arteries, including those in the arms.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Coronary Artery Disease I: Introduction01:30

Coronary Artery Disease I: Introduction

Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...