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The extracellular matrix dynamically regulates smooth muscle cell responsiveness to PDGF
E W Raines1, H Koyama, N O Carragher
1Department of Pathology, University of Washington, Seattle 98195, USA. ewraines@u.washington.edu
Abstract:
Focal accumulation of smooth muscle (SMC) within the arterial intima contributes to the formation of lesions of atherosclerosis. Platelet-derived growth factor (PDGF) is a potent stimulant of SMC migration and proliferation in culture that may play a role in the accumulation of SMC in atherogenesis. SMCs normally reside in the media of the artery wall surrounded by extracellular matrix (ECM), including type I collagen. In atherogenesis, the ECM is degraded, new ECM components, such as fibronectin, are synthesized and assembled, and these alterations in ECM components are associated with changes in SMC phenotype. To model the changes in ECM in normal and diseased arteries, we have analyzed SMCs cultured on different forms of type I collagen. Our studies demonstrate that integrin-mediated signals from various forms of type I collagen lead to specific and rapid modulation of the integrin signaling complex, including cytoskeletal connections, and of the responsiveness of SMC to PDGF stimulation.
Insights
Smooth muscle cells (SMCs) accumulate in arteries during atherosclerosis. Type I collagen affects SMCs and their response to platelet-derived growth factor (PDGF), influencing disease progression.
Area of Science:
- Vascular Biology
- Cellular Biology
- Biochemistry
Background:
- Atherosclerosis involves smooth muscle cell (SMC) accumulation in arterial intima.
- Platelet-derived growth factor (PDGF) stimulates SMC migration and proliferation, potentially contributing to atherogenesis.
- Arterial extracellular matrix (ECM) undergoes degradation and remodeling during disease, altering SMC phenotype.
Purpose of the Study:
- To model changes in ECM associated with normal and diseased arteries.
- To investigate the influence of different forms of type I collagen on SMC behavior.
- To understand how ECM composition affects SMC response to PDGF.
Main Methods:
- Culturing SMCs on various forms of type I collagen.
- Analyzing integrin-mediated signaling pathways.
- Assessing cytoskeletal connections and SMC responsiveness to PDGF.
Main Results:
- Different forms of type I collagen induce specific modulations in SMC integrin signaling.
- Integrin signals rapidly alter the SMC signaling complex and cytoskeletal organization.
- ECM composition influences SMC responsiveness to PDGF stimulation.
Conclusions:
- Type I collagen plays a critical role in regulating SMC behavior within the arterial wall.
- Integrin-mediated signaling from ECM components modulates SMC phenotype and PDGF response.
- Understanding these interactions is crucial for developing targeted therapies for atherosclerosis.