Human macrophages modulate the phenotype of cultured rabbit aortic smooth muscle cells through secretion of platelet-derived growth factor
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N Morisaki1, N Koyama, M Kawano
1Second Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Abstract:
Phenotypic change of aortic smooth muscle cells (SMC) is a key step for their abnormal proliferation in atheromatous lesions. In this study modulation of the growth properties of SMC by macrophages was investigated to clarify the mechanism regulating the SMC phenotype. Cultured rabbit SMC preincubated with either macrophages derived from human peripheral monocytes, or conditioned medium from macrophages grew faster than control SMC in the absence of either macrophages or conditioned medium. SMC preincubated with purified platelet-derived growth factor (PDGF) also grew faster than control SMC in the absence of PDGF, and their rapid growth was maintained for at least two passages. SMC preincubated with conditioned medium of macrophages plus anti-PDGF antibody did not grow faster than control SMC. Furthermore SMC preincubated with PDGF acquired the ability to secrete some mitogen, which differed from PDGF. These results suggest that macrophages modulate the phenotype of SMC by a mechanism mediated by PDGF. As a result the SMC grow faster and at the same time secrete some mitogen probably distinct from PDGF in an autocrine manner.
Insights
Macrophages influence smooth muscle cell (SMC) growth in atherosclerosis by releasing platelet-derived growth factor (PDGF). This promotes SMC proliferation and autocrine signaling, contributing to atheromatous lesions.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Atherosclerosis Research
Background:
- Phenotypic changes in aortic smooth muscle cells (SMC) are crucial for abnormal proliferation in atheromatous lesions.
- Understanding the regulation of SMC phenotype is key to addressing atherosclerosis.
Purpose of the Study:
- To investigate how macrophages modulate the growth properties of SMC.
- To elucidate the mechanism regulating SMC phenotype.
Main Methods:
- Cultured rabbit SMC were incubated with macrophages or conditioned macrophage medium.
- SMC were also incubated with purified platelet-derived growth factor (PDGF).
- The effect of anti-PDGF antibody on SMC growth was assessed.
Main Results:
- SMC incubated with macrophages or conditioned medium showed increased growth compared to controls.
- PDGF also stimulated SMC growth, with effects sustained over passages.
- Anti-PDGF antibody blocked the growth-promoting effect of macrophage-conditioned medium.
- PDGF-treated SMC acquired the ability to secrete a novel mitogen.
Conclusions:
- Macrophages modulate SMC phenotype and promote their proliferation via a PDGF-mediated mechanism.
- Activated SMC exhibit autocrine secretion of mitogens distinct from PDGF.