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Synergistic Role of Protein Phosphatase Inhibitor 1 and Sarco/Endoplasmic Reticulum Ca 2+ -ATPase in the Acquisition of the Contractile Phenotype of Arterial Smooth Muscle Cells
- Source :
- Circulation. 129:773-785
- Publication Year :
- 2014
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2014.
-
Abstract
- Background— Phenotypic modulation or switching of vascular smooth muscle cells from a contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of smooth muscle cells have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition or maintenance of the contractile phenotype modulation remains unknown. Methods and Results— In human coronary arteries, I-1 and sarco/endoplasmic reticulum Ca 2+ -ATPase expression is specific to contractile vascular smooth muscle cells. In synthetic cultured human coronary artery smooth muscle cells, protein phosphatase inhibitor 1 (I-1 target) is highly expressed, leading to a decrease in phospholamban phosphorylation, sarco/endoplasmic reticulum Ca 2+ -ATPase, and cAMP-responsive element binding activity. I-1 knockout mice lack phospholamban phosphorylation and exhibit vascular smooth muscle cell arrest in the synthetic state with excessive neointimal proliferation after carotid injury, as well as significant modifications of contractile properties and relaxant response to acetylcholine of femoral artery in vivo. Constitutively active I-1 gene transfer decreased neointimal formation in an angioplasty rat model by preventing vascular smooth muscle cell contractile to synthetic phenotype change. Conclusions— I-1 and sarco/endoplasmic reticulum Ca 2+ -ATPase synergistically induce the vascular smooth muscle cell contractile phenotype. Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders.
- Subjects :
- Male
medicine.medical_specialty
Vascular smooth muscle
chemistry.chemical_element
Aorta, Thoracic
Calcium
Biology
Muscle, Smooth, Vascular
Article
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Rats, Sprague-Dawley
Mice
Protein Phosphatase 1
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Calcium Signaling
Vascular Diseases
Mammary Arteries
Mice, Knockout
Endoplasmic reticulum
Intracellular Signaling Peptides and Proteins
Proteins
Coronary Vessels
Phenotype
Rats
Phospholamban
Femoral Artery
Mice, Inbred C57BL
medicine.anatomical_structure
Endocrinology
chemistry
Vasoconstriction
Knockout mouse
Phosphorylation
Cardiology and Cardiovascular Medicine
Artery
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 129
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....9b20a904727151517b034377e2e7f29e