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Updated: Apr 1, 2026
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Smooth Muscle-Targeted Overexpression of Peroxisome Proliferator Activated Receptor-γ Disrupts Vascular Wall
Jennifer M Kleinhenz1, Tamara C Murphy1, Anastassia P Pokutta-Paskaleva2
1Atlanta VA Medical Center, Decatur, GA, United States of America; Emory University, Atlanta, GA, United States of America.
Abstract:
Activation of the nuclear hormone receptor, PPARγ, with pharmacological agonists promotes a contractile vascular smooth muscle cell phenotype and reduces oxidative stress and cell proliferation, particularly under pathological conditions including vascular injury, restenosis, and atherosclerosis. However, pharmacological agonists activate both PPARγ-dependent and -independent mechanisms in multiple cell types confounding efforts to clarify the precise role of PPARγ in smooth muscle cell structure and function in vivo. We, therefore, designed and characterized a mouse model with smooth muscle cell-targeted PPARγ overexpression (smPPARγOE). Our results demonstrate that smPPARγOE attenuated contractile responses in aortic rings, increased aortic compliance, caused aortic dilatation, and reduced mean arterial pressure. Molecular characterization revealed that compared to littermate control mice, aortas from smPPARγOE mice expressed lower levels of contractile proteins and increased levels of adipocyte-specific transcripts. Morphological analysis demonstrated increased lipid deposition in the vascular media and in smooth muscle of extravascular tissues. In vitro adenoviral-mediated PPARγ overexpression in human aortic smooth muscle cells similarly increased adipocyte markers and lipid uptake. The findings demonstrate that smooth muscle PPARγ overexpression disrupts vascular wall structure and function, emphasizing that balanced PPARγ activity is essential for vascular smooth muscle homeostasis.
Insights
Overexpressing the nuclear hormone receptor PPARγ in smooth muscle cells disrupts vascular function, leading to aortic dilatation and reduced blood pressure. Balanced PPARγ activity is crucial for maintaining vascular smooth muscle homeostasis.
Area of Science:
- Vascular Biology
- Endocrinology
- Molecular Biology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) agonists influence vascular smooth muscle cell (VSMC) phenotype, reducing proliferation and oxidative stress.
- Pharmacological activation of PPARγ involves both dependent and independent pathways, complicating the understanding of its specific role in VSMCs in vivo.
Purpose of the Study:
- To investigate the precise role of PPARγ in VSMC structure and function.
- To create and characterize a mouse model with smooth muscle cell-specific PPARγ overexpression (smPPARγOE).
Main Methods:
- Generation of a smPPARγOE mouse model.
- Assessment of aortic ring contractile responses, compliance, and diameter.
- Molecular analysis of contractile proteins and adipocyte-specific transcripts in aortas.
- In vitro studies using adenoviral-mediated PPARγ overexpression in human aortic smooth muscle cells.
Main Results:
- smPPARγOE mice exhibited attenuated aortic contractile responses, increased aortic compliance, aortic dilatation, and reduced mean arterial pressure.
- Aortas from smPPARγOE mice showed decreased contractile protein expression and increased adipocyte-specific transcripts.
- Increased lipid deposition was observed in the vascular media and smooth muscle.
- In vitro PPARγ overexpression in human aortic smooth muscle cells led to increased adipocyte markers and lipid uptake.
Conclusions:
- Smooth muscle cell-targeted PPARγ overexpression disrupts vascular wall structure and function.
- Balanced PPARγ activity is essential for maintaining vascular smooth muscle homeostasis.
