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Anti-atherosclerotic effects of sirolimus on human vascular smooth muscle cells
- Source :
- American journal of physiology. Heart and circulatory physiology. 292(6)
- Publication Year :
- 2007
-
Abstract
- Sirolimus is a potent immunosuppressive agent and has an anti-atherosclerotic effect through its anti-proliferative property. The present study was undertaken to investigate the effect of sirolimus on intracellular cholesterol homeostasis in human vascular smooth muscle cells (VSMCs) in the presence of inflammatory cytokine IL-1β. We explored the effect of sirolimus on the lipid accumulation of VSMCs in the presence of IL-1β, using Oil Red O staining and quantitative measurement of intracellular cholesterol. The effect of sirolimus on the gene and protein expression of lipoprotein receptors and ATP binding cassettes (ABCA1 and ABCG1) was examined by real-time PCR and Western blotting, respectively. Furthermore, the effect of sirolimus on cholesterol efflux from VSMCs in the presence or absence of IL-1β was also investigated using [3H] cholesterol efflux. Finally, we examined the effect of sirolimus on the production of inflammatory cytokines in VSMCs using ELISA. Sirolimus reduced intracellular lipid accumulation in VSMCs mediated by IL-1β possibly due to the reduction of expression of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) receptors. Sirolimus increased cholesterol efflux from VSMCs and overrode the suppression of cholesterol efflux induced by IL-1β. Sirolimus also increased ABCA1 and ABCG1 genes expression, even in the presence of IL-1β. We further confirmed that sirolimus inhibited mRNA and protein expression of inflammatory cytokines IL-6, tumor necrosis factor-α, IL-8, and monocyte chemoattractant protein-1. Inhibition of lipid uptake together with increasing cholesterol efflux and the inhibition of inflammatory cytokines are all important aspects of the anti-atherosclerotic effects of sirolimus on VSMCs.
- Subjects :
- Apolipoprotein E
Very low-density lipoprotein
Vascular smooth muscle
Physiology
Interleukin-1beta
Myocytes, Smooth Muscle
Gene Expression
Pharmacology
Muscle, Smooth, Vascular
Proinflammatory cytokine
chemistry.chemical_compound
Physiology (medical)
medicine
Homeostasis
Humans
cardiovascular diseases
RNA, Messenger
Coloring Agents
Cells, Cultured
ATP Binding Cassette Transporter, Subfamily G, Member 1
Inflammation
Sirolimus
biology
Dose-Response Relationship, Drug
Staining and Labeling
Cholesterol
Cardiovascular Agents
equipment and supplies
Atherosclerosis
Coronary Vessels
surgical procedures, operative
chemistry
Biochemistry
Receptors, LDL
ABCA1
Cardiovascular agent
cardiovascular system
biology.protein
Cytokines
lipids (amino acids, peptides, and proteins)
ATP-Binding Cassette Transporters
Cardiology and Cardiovascular Medicine
Azo Compounds
medicine.drug
ATP Binding Cassette Transporter 1
Subjects
Details
- ISSN :
- 03636135
- Volume :
- 292
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Accession number :
- edsair.doi.dedup.....9c26dd5e0d9fa0e3e2d124afa307b2e4