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Updated: May 14, 2026
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress
Joshua K Salabei1, Timothy D Cummins, Mahavir Singh
1Diabetes and Obesity Center and Institute of Molecular Cardiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Abstract:
Vascular injury and chronic arterial diseases result in exposure of VSMCs (vascular smooth muscle cells) to increased concentrations of growth factors. The mechanisms by which growth factors trigger VSMC phenotype transitions remain unclear. Because cellular reprogramming initiated by growth factors requires not only the induction of genes involved in cell proliferation, but also the removal of contractile proteins, we hypothesized that autophagy is an essential modulator of VSMC phenotype. Treatment of VSMCs with PDGF (platelet-derived growth factor)-BB resulted in decreased expression of the contractile phenotype markers calponin and α-smooth muscle actin and up-regulation of the synthetic phenotype markers osteopontin and vimentin. Autophagy, as assessed by LC3 (microtubule-associated protein light chain 3 α; also known as MAP1LC3A)-II abundance, LC3 puncta formation and electron microscopy, was activated by PDGF exposure. Inhibition of autophagy with 3-methyladenine, spautin-1 or bafilomycin stabilized the contractile phenotype. In particular, spautin-1 stabilized α-smooth muscle cell actin and calponin in PDGF-treated cells and prevented actin filament disorganization, diminished production of extracellular matrix, and abrogated VSMC hyperproliferation and migration. Treatment of cells with PDGF prevented protein damage and cell death caused by exposure to the lipid peroxidation product 4-hydroxynonenal. The results of the present study demonstrate a distinct form of autophagy induced by PDGF that is essential for attaining the synthetic phenotype and for survival under the conditions of high oxidative stress found to occur in vascular lesions.
Insights
Autophagy modulates vascular smooth muscle cell (VSMC) phenotype transitions. Platelet-derived growth factor (PDGF) activates autophagy, promoting VSMC synthetic phenotype and survival during vascular injury.
Area of Science:
- Vascular Biology
- Cellular Biology
- Autophagy Research
Background:
- Vascular smooth muscle cells (VSMCs) undergo phenotype changes in response to growth factors during vascular injury.
- The precise mechanisms driving VSMC phenotype transitions, particularly the role of autophagy, are not fully understood.
Purpose of the Study:
- To investigate the role of autophagy in mediating vascular smooth muscle cell (VSMC) phenotype transitions induced by growth factors.
- To determine if autophagy is essential for VSMC adaptation and survival under conditions of oxidative stress associated with vascular disease.
Main Methods:
- VSMCs were treated with platelet-derived growth factor (PDGF)-BB to induce phenotype changes.
- Autophagy activation was assessed using LC3-II abundance, LC3 puncta formation, and electron microscopy.
- Autophagy inhibition was achieved using 3-methyladenine, spautin-1, and bafilomycin.
Main Results:
- PDGF-BB treatment decreased contractile markers (calponin, α-smooth muscle actin) and increased synthetic markers (osteopontin, vimentin) in VSMCs.
- PDGF exposure activated autophagy, which was inhibited by specific autophagy inhibitors, stabilizing the contractile phenotype.
- Inhibition of autophagy prevented VSMC hyperproliferation, migration, and protected against PDGF-induced protein damage and cell death.
Conclusions:
- Platelet-derived growth factor (PDGF) induces a specific form of autophagy essential for vascular smooth muscle cell (VSMC) synthetic phenotype acquisition.
- Autophagy plays a critical role in VSMC survival under the oxidative stress conditions prevalent in vascular lesions.
- Targeting autophagy may offer a therapeutic strategy for managing vascular diseases characterized by VSMC dysfunction.
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