Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist.

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Abstract Text:

Sabine Rehm,Roberta A Thomas,Kim S Smith,Rosanna C Mirabile,Tracy L Gales,Scot L Eustis,Rogely W Boyce,Sabine Rehm,Roberta A Thomas,Kim S Smith,Rosanna C Mirabile,Tracy L Gales,Scot L Eustis,Rogely W Boyce,Sabine Rehm,Roberta A Thomas,Kim S Smith,Rosanna C Mirabile,Tracy L Gales,Scot L Eustis,Rogely W Boyce,

Novel vascular lesions were observed in mice given an alpha vbeta 3, alpha vbeta 5 receptor antagonist (SB-273005) for up to 3 months. Vascular smooth muscle cell (VSMC) necrosis was observed in aorta and renal hilar arteries approximately 6 hours after dosing followed by loss of VSMC, adaptive medial thickening by VSMC hypertrophy and deposition of PAS-positive matrix and collagen. Renal hilar and arcuate arteries developed delayed and transient fibrinoid necrosis and inflammation. Vascular regeneration was not evident following drug-withdrawal after 3 days of dosing. Vascular lesions were associated with necrosis, regeneration and fibrosis of heart, kidney and spleen consistent with initial ischemic injury followed by tissue repair. VSMC toxicity was likely not related to integrin antagonism because lesions were not observed with related compounds and no vascular changes were observed in other preclinical species. In vitro studies failed to demonstrate a direct toxic effect of SB-273005 on VSMC or unique species sensitivity of murine VSMC. In conclusion, SB-273005 caused VSMC necrosis in aorta and renal arteries of mice. Lesions did not progress or recover, but there was medial hypertrophic adaptation even with continued dosing. This is considered direct species-specific VSMC toxicity of unknown mechanism and unrelated to vitronectin receptor antagonism.

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Publishing Authors By Initials

S Rehm,RA Thomas,KS Smith,RC Mirabile,TL Gales,SL Eustis,RW Boyce,S Rehm,RA Thomas,KS Smith,RC Mirabile,TL Gales,SL Eustis,RW Boyce,S Rehm,RA Thomas,KS Smith,RC Mirabile,TL Gales,SL Eustis,RW Boyce,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Toxicologic pathology

VOLUME: 35

Page Numbers: 958-71

Journal Abbreviation:

ISSN: 0192-6233

DAY: 21

MONTH: 12

YEAR: 2007

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7905907

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist.

AFFILIATION: GlaxoSmithKline, King of Prussia, PA, USA.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Toxicol Pathol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist Related Publications

• Assessment of an automated bioreactor to propagate and harvest keratinocytes for fabrication of engineered skin substitutes.
• Changes in education.
• Children's memory for a mild stressor: the role of sympathetic activation and parasympathetic withdrawal.
• Chiral building blocks: enantioselective syntheses of benzyloxymethyl phenyl propionic acids.
• CysLT2 receptors interact with CysLT1 receptors and down-modulate cysteinyl leukotriene dependent mitogenic responses of mast cells.
• Decoration of Pasteurella multocida lipopolysaccharide with phosphocholine is important for virulence.
• Determination of additives and organic contaminants in food by CE and CEC.
• Earth monitoring: Vigilance is not enough.
• Fiber density of electrospun gelatin scaffolds regulates morphogenesis of dermal-epidermal skin substitutes.
• High cut-off point membranes in septic acute renal failure: A systematic review.
• Individual and collective exposure to political violence: Palestinian adolescents coping with conflict.
• Influence of electrospun collagen on wound contraction of engineered skin substitutes.
• Injury in Canadian youth: a brief report from the Health Behaviour in School-Aged Children Survey.
• Landscape heterogeneity shapes predation in a newly restored predator-prey system.
• Lysophospholipids as mediators of immunity.
• NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1.
• Novel vascular lesions in mice given a non-Peptide vitronectin receptor antagonist.
• Objectives in the Programming of Post-war Sanitation Works.
• Pattern transformation triggered by deformation.
• Preliminary Report of the Sub-Committee on Educational Qualifications of Public Health Engineers.
• Preliminary Report of the Sub-Committee on Educational Qualifications of Sanitarians.
• Restructuring the multi-professional organization: professional identity and adjustment to change in a public hospital.
• Social stratification, health, and violence in the very young.
• Survival of skin graft in mycosis fungoides - a solution for a management dilemma.
• Synthesis of chiral building blocks for use in drug discovery.
• The tao of conscience: conflict and resolution.
• Thyroid function testing in elephant seals in health and disease.
• Willow on Yellowstone's northern range: evidence for a trophic cascade?
• [OBSERVATIONS ON FLUORIDATION OF WATER.]
• [Professional aspects of engineering.]