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Updated: Aug 5, 2026
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Bortezomib Suppresses Abnormal Proliferation, Migration, and Phenotypic Switching of Aortic Smooth Muscle Cells
Yu-Hsin Tseng1, Lin-Yen Wang2,3,4,5, Yu-Hsin Kuan6
1Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung.
Background:
Atherosclerosis is the leading cause of cardiovascular disease and mortality worldwide. The proliferation, migration, and phenotypic switching of vascular smooth muscle cells are central to its pathogenesis. Bortezomib, the first Food and Drug Administration-approved proteasome inhibitor for multiple myeloma, suppresses the proliferation and migration of pulmonary artery smooth muscle cells. However, its effects on aortic vascular smooth muscle cells (AoSMCs) remain unclear.
Methods:
Rat AoSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) or angiotensin II (Ang II), with or without bortezomib. Cytotoxicity, proliferation, and migration were assessed by MTT, wound healing, and Boyden chamber assays. Intracellular and mitochondrial ROS were measured by DCFH-DA and MitoSOX. mRNA and protein levels of bone morphogenetic protein-2 (BMP-2), Runt-related transcription factor 2 (Runx2), α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (ERK), and phosphorylated protein kinase B (Akt) were assessed by RT-qPCR and Western blotting. Calcium deposition was assessed using Alizarin Red S staining.
Results:
Bortezomib attenuated PDGF-BB and Ang II-induced proliferation and migration of AoSMCs accompanied by reduced ROS production and decreased phosphorylation of ERK and Akt. Furthermore, bortezomib suppressed PDGF-BB- and Ang II-induced osteogenic markers (BMP-2 and Runx2) and calcium deposition, while restoring the contractile marker α-SMA, which was inhibited by PDGF-BB and Ang II.
Conclusions:
Bortezomib attenuated PDGF-BB- and Ang II-induced proliferation, migration, and phenotypic switching of AoSMCs, potentially through reduced ROS production. Mechanistically, bortezomib inhibited ERK and Akt phosphorylation and restored a contractile phenotype. These findings suggest that proteasome inhibition may offer a novel therapeutic approach to modulate vascular remodeling in atherosclerosis.
Insights
Bortezomib, a proteasome inhibitor, reduces proliferation and migration of aortic smooth muscle cells by decreasing ROS production and restoring contractile markers. This suggests proteasome inhibition as a potential therapy for atherosclerosis.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pharmacology
Background:
- Atherosclerosis is a major global health issue driven by vascular smooth muscle cell (VSMC) dysfunction.
- Bortezomib, a proteasome inhibitor, is approved for multiple myeloma and known to affect pulmonary artery smooth muscle cells.
- The impact of bortezomib on aortic vascular smooth muscle cells (AoSMCs) in atherosclerosis is not well understood.
Purpose of the Study:
- To investigate the effects of bortezomib on platelet-derived growth factor-BB (PDGF-BB) and angiotensin II (Ang II)-stimulated AoSMCs.
- To determine if bortezomib can modulate key pathological processes in AoSMCs relevant to atherosclerosis.
Main Methods:
- AoSMCs were stimulated with PDGF-BB or Ang II, with or without bortezomib.
- Proliferation, migration, reactive oxygen species (ROS) production, and osteogenic/contractile marker expression were assessed.
- Key signaling pathways (ERK, Akt) and calcium deposition were analyzed.
Main Results:
- Bortezomib significantly reduced PDGF-BB and Ang II-induced AoSMC proliferation and migration.
- Bortezomib decreased ROS production and inhibited ERK and Akt phosphorylation.
- Bortezomib suppressed osteogenic markers (BMP-2, Runx2) and calcium deposition while restoring α-SMA.
Conclusions:
- Bortezomib attenuates proliferation, migration, and phenotypic switching in AoSMCs, potentially via reduced ROS.
- The mechanism involves inhibition of ERK and Akt signaling, promoting a contractile phenotype.
- Proteasome inhibition represents a potential therapeutic strategy for vascular remodeling in atherosclerosis.
