| Parathyroid-hormone-related protein as a regulator of pRb and the cell cycle in arterial smooth muscle. | |
| | |
MedLine Citation:
|
PMID: 15210588 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Parathyroid hormone-related protein (PTHrP), a normal product of arterial vascular smooth muscle (VSM), contains a nuclear localization signal (NLS) and at least 2 translational initiation sites, one that generates a conventional signal peptide and one that disrupts the signal peptide. These unusual features allow PTHrP either to be secreted in a paracrine/autocrine fashion, and thereby to inhibit arterial smooth muscle proliferation, or to be retained within the cytosol and to translocate into the nucleus, thereby serving as an intracrine stimulator of smooth muscle proliferation. METHODS AND RESULTS: Here, we demonstrate 2 important findings. First, PTHrP dramatically increases the percentage of VSM cells in the S and in G2/M phases of the cell cycle. These effects require critical serine and threonine residues at positions Ser119, Ser130, Thr132, and Ser138 in the carboxy-terminus of PTHrP and are associated with the phosphorylation of the key cell cycle checkpoint regulator retinoblastoma protein, pRb. Second, because PTHrP devoid of the NLS serves as an inhibitor of VSM proliferation, we hypothesized that local delivery of NLS-deleted PTHrP to the arterial wall at the time of angioplasty might prevent neointimal hyperplasia. As hypothesized, using a rat carotid angioplasty model, adenoviral delivery of NLS-deleted PTHrP completely abolished the development of the neointima after angioplasty. CONCLUSIONS: PTHrP interacts with key cell cycle regulatory pathways within the arterial wall. Moreover, NLS-deleted PTHrP delivered to the arterial wall at the time of angioplasty seems to have promise as an agent that could reduce or eliminate the neointimal response to angioplasty. |
| | |
Authors:
|
Nathalie Fiaschi-Taesch; Karen K Takane; Sophia Masters; Juan Carlos Lopez-Talavera; Andrew F Stewart |
Related Documents
:
|
1531358 - Resolution of petrous internal carotid artery stenosis after transluminal angioplasty. ... 8009408 - Tissue plasminogen activator thrombolysis and transluminal angioplasty in the treatment... 19624078 - Atherectomy for infrainguinal peripheral artery disease. 2868798 - Percutaneous angioplasty of internal mammary artery graft stenosis: case report and dis... 1707818 - Relaxation response of isolated canine veins to agents that act on the adenylate cyclas... 12422118 - Percutaneous transhepatic treatment of symptomatic mesenteric venous thrombosis. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2004-06-21 |
Journal Detail:
|
Title: Circulation Volume: 110 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2004 Jul |
Date Detail:
|
Created Date: 2004-07-13 Completed Date: 2005-01-10 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 177-85 Citation Subset: AIM; IM |
Affiliation:
|
Division of Endocrinology and Metabolism, BST E-1140, Endocrinology, University of Pittsburgh School of Medicine, 3550 Terrace St, Pittsburgh, PA 15213, USA. taeschn@msx.dept-med.pitt.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenoviridae
/
genetics Angioplasty, Balloon / adverse effects Animals Aorta, Thoracic Carotid Artery Injuries / therapy Carotid Artery, Common Cell Cycle / drug effects, physiology Cell Division Cell Line / cytology, drug effects DNA, Complementary / genetics Gene Therapy Genetic Vectors / administration & dosage, therapeutic use Male Muscle, Smooth, Vascular / pathology Myocytes, Smooth Muscle / cytology, drug effects Parathyroid Hormone-Related Protein / chemistry, genetics, physiology* Peptide Fragments / physiology Phosphorylation Phosphoserine / analysis Phosphothreonine / analysis Protein Processing, Post-Translational Protein Transport Rats Rats, Sprague-Dawley Retinoblastoma Protein / physiology* Transfection |
| Grant Support | |
ID/Acronym/Agency:
|
R-01-54308//PHS HHS |
| Chemical | |
Reg. No./Substance:
|
0/DNA, Complementary; 0/Parathyroid Hormone-Related Protein; 0/Peptide Fragments; 0/Retinoblastoma Protein; 1114-81-4/Phosphothreonine; 17885-08-4/Phosphoserine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Molecular imaging of factor XIIIa activity in thrombosis using a novel, near-infrared fluorescent co...
Next Document: Plasma B-type natriuretic peptide levels predict postoperative atrial fibrillation in patients under...