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Updated: Jul 25, 2025
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Network Preservation Analysis Reveals Dysregulated Metabolic Pathways in Human Vascular Smooth Muscle Cell Phenotypic
R Noah Perry1,2, Diana Albarracin2, Redouane Aherrahrou1
1Center for Public Health Genomics (R.N.P., R.A., M.C.), University of Virginia, Charlottesville.
Background:
Vascular smooth muscle cells are key players involved in atherosclerosis, the underlying cause of coronary artery disease. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. An in-depth characterization of their gene regulatory networks can help better understand how their dysfunction may impact disease progression.
Methods:
We conducted a gene expression network preservation analysis in aortic smooth muscle cells isolated from 151 multiethnic heart transplant donors cultured under quiescent or proliferative conditions.
Results:
We identified 86 groups of coexpressed genes (modules) across the 2 conditions and focused on the 18 modules that are least preserved between the phenotypic conditions. Three of these modules were significantly enriched for genes belonging to proliferation, migration, cell adhesion, and cell differentiation pathways, characteristic of phenotypically modulated proliferative vascular smooth muscle cells. The majority of the modules, however, were enriched for metabolic pathways consisting of both nitrogen-related and glycolysis-related processes. Therefore, we explored correlations between nitrogen metabolism-related genes and coronary artery disease-associated genes and found significant correlations, suggesting the involvement of the nitrogen metabolism pathway in coronary artery disease pathogenesis. We also created gene regulatory networks enriched for genes in glycolysis and predicted key regulatory genes driving glycolysis dysregulation.
Conclusions:
Our work suggests that dysregulation of vascular smooth muscle cell metabolism participates in phenotypic transitioning, which may contribute to disease progression, and suggests that AMT (aminomethyltransferase) and MPI (mannose phosphate isomerase) may play an important role in regulating nitrogen and glycolysis-related metabolism in smooth muscle cells.
Insights
Vascular smooth muscle cell metabolic dysregulation, particularly in nitrogen and glycolysis pathways, contributes to coronary artery disease progression. Key regulators like aminomethyltransferase (AMT) and mannose phosphate isomerase (MPI) are implicated.
Area of Science:
- Cardiovascular Biology
- Molecular Metabolism
- Atherosclerosis Research
Background:
- Vascular smooth muscle cells (VSMCs) are critical in atherosclerosis, with roles influenced by their phenotypic state.
- Understanding VSMC gene regulatory networks is vital for elucidating their role in disease progression.
Purpose of the Study:
- To analyze gene expression networks in VSMCs under different culture conditions.
- To identify key metabolic pathways and regulatory genes involved in VSMC phenotypic changes relevant to coronary artery disease (CAD).
Main Methods:
- Gene expression network preservation analysis was performed on aortic smooth muscle cells from heart transplant donors.
- Comparative analysis of gene modules under quiescent versus proliferative conditions.
Main Results:
- Identified 86 gene coexpression modules, with 18 showing significant differences between conditions.
- Modules related to proliferation and cell adhesion were noted, but most were enriched in nitrogen metabolism and glycolysis pathways.
- Significant correlations were found between nitrogen metabolism genes and CAD-associated genes.
Conclusions:
- VSMC metabolic dysregulation, particularly in nitrogen and glycolysis pathways, contributes to phenotypic changes and disease progression.
- Aminomethyltransferase (AMT) and Mannose Phosphate Isomerase (MPI) are suggested as key regulators of these metabolic pathways in VSMCs.
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