Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization
J N Wilcox1, K M Smith, L T Williams
1Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080.
Abstract:
Platelet-derived growth factor (PDGF) mRNA, and mRNA for its receptor, have been localized to specific cell types within the human atherosclerotic plaque, using in situ hybridization. The predominant cell types found to express PDGF A and B chain mRNA are mesenchymal-appearing intimal cells and endothelial cells, respectively, with little or no expression detected in macrophages. The distribution of PDGF receptor mRNA containing cells was also examined and found to be localized predominantly in the plaque intima.
Insights
Platelet-derived growth factor (PDGF) mRNA and its receptor are found in specific cells within human atherosclerotic plaques. Mesenchymal intimal cells and endothelial cells express PDGF, but not typically macrophages, indicating localized signaling in atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Pathology
- Atherosclerosis Research
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- Platelet-derived growth factor (PDGF) plays a role in cell growth and migration relevant to vascular diseases.
- Understanding the cellular sources and localization of PDGF within atherosclerotic plaques is crucial for therapeutic development.
Purpose of the Study:
- To investigate the cellular localization of Platelet-Derived Growth Factor (PDGF) mRNA and its receptor mRNA within human atherosclerotic plaques.
- To identify the specific cell types responsible for PDGF production and signaling within the plaque microenvironment.
- To determine the distribution of PDGF receptor expression in relation to plaque components.
Main Methods:
- Utilized in situ hybridization techniques to detect and localize specific mRNA transcripts.
- Examined tissue sections from human atherosclerotic plaques.
- Quantified and identified cell types expressing PDGF A-chain mRNA, PDGF B-chain mRNA, and PDGF receptor mRNA.
Main Results:
- PDGF A-chain mRNA was predominantly expressed by mesenchymal-appearing intimal cells.
- PDGF B-chain mRNA was primarily localized to endothelial cells within the plaque.
- Little to no PDGF mRNA expression was detected in plaque macrophages.
- PDGF receptor mRNA-containing cells were predominantly found within the plaque intima.
Conclusions:
- Specific cell types within the human atherosclerotic plaque, namely intimal cells and endothelial cells, are sources of PDGF mRNA.
- Macrophages within the plaque show minimal expression of PDGF mRNA.
- The PDGF receptor is also localized within the plaque intima, suggesting autocrine or paracrine signaling loops.
- These findings highlight the localized nature of PDGF signaling in atherosclerosis and its potential role in plaque development.
