Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events.

Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Research Abstract Details 

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Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Abstract Text:

Jocelyn N Clark-Greuel,Jeanne M Connolly,Elizabeth Sorichillo,Navneet R Narula,H Scott Rapoport,Emile R Mohler,Joseph H Gorman,Robert C Gorman,Robert J Levy,

BACKGROUND: Aortic valve stenosis is the most frequent indication for valve replacement surgery, and is commonly associated with pathologic calcification. Previous investigations by our group have shown a strong association of transforming growth factor-beta1 (TGF-beta1)-related mechanisms with calcific aortic stenosis in both cell culture and clinical pathology studies. METHODS: In the present investigations we sought to investigate the sequence of events involved in TGF-beta1-initiated aortic valve interstitial cell calcification in cell culture, and to study related gene expression pattern differences comparing calcific aortic stenosis surgical specimens with normal aortic valve leaflets. RESULTS: Sheep aortic valve interstitial cells (SAVIC) in culture progressively calcified over 14 days after the addition of TGF-beta1 to a significantly greater extent than non-TGF-beta1 controls. The TGF-beta1-induced SAVIC calcification was associated with maximal levels of alkaline phosphatase by 72 hours. Annexin V positive apoptosis was increased in TGF-beta1-treated SAVIC cultures at 14 days compared with controls. Matrix metalloproteinase 9 per gel zymography was detectable only in SAVIC cultures treated with TGF-beta1 from seven days on. Matrix metalloproteinase 2 was present in all SAVIC cultures per gel zymograms, either with or without TGF-beta1, but the active form of matrix metalloproteinase 2 significantly increased over 14 days in response to TGF-beta1. Quantitative gene expression studies (re: RNA levels) of human aortic valve cusps obtained at cardiac surgery demonstrated a number of related trends, including upregulation of the expression of TGF-beta1, alkaline phosphatase, and matrix metalloproteinase 9 in calcified human aortic valves. CONCLUSIONS: Transforming growth factor-beta1 causes SAVIC to calcify due to an early maximal increase in alkaline phosphatase activity with associated apoptotic events and increased matrix metalloproteinase 9. These TGF-beta1-related mechanistic events may be of clinical relevance based upon the gene expression pattern changes observed in calcific aortic stenosis valve cusps.

Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Publishing Authors By Initials

JN Clark-Greuel,JM Connolly,E Sorichillo,NR Narula,HS Rapoport,ER Mohler,JH Gorman,RC Gorman,RJ Levy,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research

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Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Annals of thoracic surgery

VOLUME: 83

Page Numbers: 946-53

Journal Abbreviation: Ann. Thorac. Surg.

ISSN: 1552-6259

DAY: 3

MONTH: Mar

YEAR: 2007

Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 15030100

Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta1

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Information

Substance Name: Matrix Metalloproteinase 9

Registry Number: EC 3.4.24.35

Grant and Affiliation Information for Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events.

AFFILIATION: Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA.

Country: Netherlands

AGENCY: United States NHLBI

GRANT: T32-HL07954

ACRONYM: HL

MEDLINETA: Ann Thorac Surg

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