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Updated: Jan 14, 2026
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Differential gene expression in peripheral vascular smooth muscle cells of patients with peripheral artery disease
Dongoh Lee1, Ji Hye Kim2, Dong Yeon Lee3
1SNU Seoul Hospital, Seoul, Korea.
Insights
Peripheral vascular smooth muscle cells (VSMCs) in critical limb ischemia (CLI) show altered gene expression, particularly UNC5B, which is overexpressed under calcifying conditions. This contrasts with normal aortic VSMCs, suggesting a novel role in vascular calcification.
Area of Science:
- Vascular Biology
- Genomics
- Cardiovascular Research
Background:
- Peripheral vascular smooth muscle cells (VSMCs) role in vascular calcification is understudied compared to major VSMCs.
- Critical limb ischemia (CLI) in patients with Chronic Kidney Disease (CKD) presents a unique context for studying peripheral VSMCs.
- Investigating differentially expressed genes (DEGs) in peripheral VSMCs from CLI patients is crucial.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in peripheral VSMCs from patients with CLI.
- To compare gene expression profiles of peripheral VSMCs from CKD patients with normal aortic VSMCs.
- To elucidate the role of specific genes in vascular calcification.
Main Methods:
- Peripheral VSMCs isolated from posterior tibial arteries of 6 CKD patients with CLI.
- Culturing VSMCs in normal and high phosphate media for 10 days.
- mRNA sequencing and bioinformatics analysis of DEGs, focusing on contractile and synthetic phenotypes.
Main Results:
- Contractility genes (ACTA2, CALD1, CNN1, TAGLN) increased in control VSMCs, not in pathological ones.
- Synthetic phenotype genes (ICAM1, SPP1, MMP3, TIMP1) showed no significant changes or decreases.
- UNC5B expression was uniquely upregulated in pathological peripheral VSMCs under calcifying conditions.
Conclusions:
- UNC5B is overexpressed in pathological peripheral VSMCs during calcification, unlike normal aortic VSMCs.
- This suggests a specific role for UNC5B in peripheral VSMC calcification.
- Further investigation into UNC5B's function in peripheral VSMCs is warranted.
Background:
The role of peripheral vascular smooth muscle cells (VSMCs) in vascular calcification has been overlooked compared with that of the major VSMCs. This study aimed to investigate the differentially expressed genes (DEGs) of peripheral VSMCs in patients with critical limb ischemia (CLI) results from peripheral arterial disease and Chronic Kidney disease (CKD).
Methods:
We isolated peripheral VSMCs from the posterior tibial artery of 6 patients with CKD who underwent below-knee amputation for CLI. Using normal human aortic VSMCs as a control, we cultured all samples in normal and high phosphate media for 10 days. Total RNA was extracted and analyzed using mRNA sequencing. Expression levels of genes related to contractile and synthetic phenotypes were examined. Bioinformatics analysis of the DEGs was performed.
Results:
All four genes (ACTA2, CALD1, CNN1, and TAGLN) related to the contractility phenotype increased only in the control group. The expression of all four genes (ICAM1, SPP1, MMP3, and TIMP1) related to the synthetic phenotype showed no significant changes or decreases in all samples. Several genes (SERTAD4, ITGA11, SPRN, IGFBP6, BCL2A1, APOE, TRABD2A, and FAM13B) showed significant changes under calcifying conditions. Only UNC5B expression showed an opposite pattern between normal human aortic VSMC and pathological peripheral VSMCs.
Conclusions:
UNC5B was overexpressed only in pathologic peripheral VSMCs under calcifying conditions, whereas downregulated in normal aortic VSMCs. Further research on the effect of UNC5B on peripheral VSMC is warranted. (IRB number: H-1711-022-897).
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