Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression

Autor: Marion J.J. Gijbels, Marjan Smook, Philip Gotwals, Victor E. Koteliansky, Peter Heeringa, Esther Lutgens, Mat J.A.P. Daemen
Přispěvatelé: Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Other departments
Jazyk: angličtina
Rok vydání: 2002
Předmět:
Male
Pathology
FACTOR-BETA-1
Apolipoprotein B
Arteriosclerosis
DISEASE
Pathogenesis
ATHEROSCLEROTIC LESIONS
Transforming Growth Factor beta
Fibrosis
Carotid Stenosis
Receptor
GENE-EXPRESSION
biology
TGF-BETA
Phenotype
Disease Progression
CAROTID ATHEROSCLEROSIS
medicine.symptom
Cardiology and Cardiovascular Medicine
Signal Transduction
medicine.medical_specialty
Recombinant Fusion Proteins
INHIBITION
Inflammation
Protein Serine-Threonine Kinases
Drug Administration Schedule
Apolipoproteins E
Internal medicine
TGF beta signaling pathway
medicine
Animals
RECEPTOR
fibrosis
Receptor
Transforming Growth Factor-beta Type II
Transforming growth factor beta
medicine.disease
Mice
Mutant Strains
Immunoglobulin Fc Fragments
Mice
Inbred C57BL
MICE
Endocrinology
Solubility
inflammation
Immunoglobulin G
transforming growth factor-beta
CELLS
biology.protein
atherosclerosis
Receptors
Transforming Growth Factor beta
Transforming growth factor
Zdroj: Arteriosclerosis thrombosis and vascular biology, 22(6), 975-982. LIPPINCOTT WILLIAMS & WILKINS
Arteriosclerosis, thrombosis, and vascular biology, 22(6), 975-982. Lippincott Williams and Wilkins
ISSN: 1079-5642
DOI: 10.1161/01.atv.0000019729.39500.2f
Popis: The transition from stable to rupture-prone and ruptured atherosclerotic plaques involves many processes, including an altered balance between inflammation and fibrosis. An important mediator of both is transforming growth factor (TGF)-beta, and a pivotal role for TGF-beta in atherogenesis has been postulated. Here, we determine the in vivo effects of TGF-beta inhibition on plaque progression and phenotype in atherosclerosis. Recombinant soluble TGF-beta receptor II (TGFbetaRII:Fc), which inhibits TGF-beta signaling, was injected in apolipoprotein E-deficient mice for 12 weeks (50 mug, twice a week intraperitoneally) as early treatment (treatment age 5 to 17 weeks) and delayed treatment (age 17 to 29 weeks). In the early treatment group, inhibition of TGF-beta signaling treatment resulted in a prominent increase in CD3- and CD45-positive cells in atherosclerotic lesions. Most profound effects were found in the delayed treatment group. Plaque area decreased 37.5% after TGFbetaRII:Fc treatment. Moreover, plaque morphology changed into an inflammatory phenotype that was low in fibrosis: lipid cores were 64.6% larger, and inflammatory cell content had increased 2.7-fold. The amount of fibrosis decreased 49.6%, and intraplaque hemorrhages and iron and fibrin deposition were observed frequently. TGFbetaRII:Fc treatment did not result in systemic effects. These results reveal a pivotal role for TGF-beta in the maintenance of the balance between inflammation and fibrosis in atherosclerotic plaques.
Databáze: OpenAIRE
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