Proteomic alterations in heat shock protein 27 and identification of phosphoproteins in ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve

Peter Matt, Zongming Fu, Thierry Carrel, David L. Huso, Stefan Dirnhofer, Ivan Lefkovits, Hans Reinhard Zerkowski, Jennifer E. Van Eyk

Research output: Contribution to journalArticle

Abstract

Whether or not there are molecular differences, at the intra- and extracellular level, between aortic dilatation in patients with bicuspid (BAV) and those with a tricuspid aortic valve (TAV) has remained controversial for years. We have performed 2-dimensional gel electrophoresis and mass spectrometry coupled with dephosphorylation and phosphostaining experiments to reveal and define protein alterations and the high abundant structural phosphoproteins in BAV compared to TAV aortic aneurysm samples. 2-D gel patterns showed a high correlation in protein expression between BAV and TAV specimens (n = 10). Few proteins showed significant differences, among those a phosphorylated form of heat shock protein (HSP) 27 with significantly lower expression in BAV compared to TAV aortic samples (p = 0.02). The phosphoprotein tracing revealed four different phosphoproteins including Rho GDP dissociation inhibitor 1, calponin 3, myosin regulatory light chain 2 and four differentially phosphorylated forms of HSP27. Levels of total HSP27 and dually phosphorylated HSP27 (S78/S82) were investigated in an extended patient cohort (n = 15) using ELISA. Total HSP27 was significantly lower in BAV compared to TAV patients (p = 0.03), with no correlation in levels of phospho-HSP27 (S78/S82) (p = 0.4). Western blots analysis showed a trend towards lower levels of phospho-HSP27 (S78) in BAV patients (p = 0.07). Immunohistochemical analysis revealed that differences in HSP27 occur in the cytoplasma of VSMC's and not extracellularly. Alterations in HSP27 may give early evidence for intracellular differences in aortic aneurysm of patients with BAV and TAV. Whether HSP27 and the defined phosphoproteins have a specific role in BAV associated aortic dilatation remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)792-801
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume43
Issue number6
DOIs
StatePublished - Dec 2007

Fingerprint

HSP27 Heat-Shock Proteins
Tricuspid Valve
Aortic Aneurysm
Phosphoproteins
Aortic Valve
Proteomics
rho Guanine Nucleotide Dissociation Inhibitor alpha
Dilatation
Gels
Myosin Light Chains
Proteins
Bicuspid
Electrophoresis
Bicuspid Aortic Valve
Mass Spectrometry
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • Aortic aneurysm
  • Bicuspid aortic valve
  • Heat shock protein 27
  • Phosphoprotein
  • Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Proteomic alterations in heat shock protein 27 and identification of phosphoproteins in ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve. / Matt, Peter; Fu, Zongming; Carrel, Thierry; Huso, David L.; Dirnhofer, Stefan; Lefkovits, Ivan; Zerkowski, Hans Reinhard; Van Eyk, Jennifer E.

In: Journal of Molecular and Cellular Cardiology, Vol. 43, No. 6, 12.2007, p. 792-801.

Research output: Contribution to journalArticle

Matt, Peter ; Fu, Zongming ; Carrel, Thierry ; Huso, David L. ; Dirnhofer, Stefan ; Lefkovits, Ivan ; Zerkowski, Hans Reinhard ; Van Eyk, Jennifer E. / Proteomic alterations in heat shock protein 27 and identification of phosphoproteins in ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve. In: Journal of Molecular and Cellular Cardiology. 2007 ; Vol. 43, No. 6. pp. 792-801.
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AU - Carrel, Thierry

AU - Huso, David L.

AU - Dirnhofer, Stefan

AU - Lefkovits, Ivan

AU - Zerkowski, Hans Reinhard

AU - Van Eyk, Jennifer E.

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AB - Whether or not there are molecular differences, at the intra- and extracellular level, between aortic dilatation in patients with bicuspid (BAV) and those with a tricuspid aortic valve (TAV) has remained controversial for years. We have performed 2-dimensional gel electrophoresis and mass spectrometry coupled with dephosphorylation and phosphostaining experiments to reveal and define protein alterations and the high abundant structural phosphoproteins in BAV compared to TAV aortic aneurysm samples. 2-D gel patterns showed a high correlation in protein expression between BAV and TAV specimens (n = 10). Few proteins showed significant differences, among those a phosphorylated form of heat shock protein (HSP) 27 with significantly lower expression in BAV compared to TAV aortic samples (p = 0.02). The phosphoprotein tracing revealed four different phosphoproteins including Rho GDP dissociation inhibitor 1, calponin 3, myosin regulatory light chain 2 and four differentially phosphorylated forms of HSP27. Levels of total HSP27 and dually phosphorylated HSP27 (S78/S82) were investigated in an extended patient cohort (n = 15) using ELISA. Total HSP27 was significantly lower in BAV compared to TAV patients (p = 0.03), with no correlation in levels of phospho-HSP27 (S78/S82) (p = 0.4). Western blots analysis showed a trend towards lower levels of phospho-HSP27 (S78) in BAV patients (p = 0.07). Immunohistochemical analysis revealed that differences in HSP27 occur in the cytoplasma of VSMC's and not extracellularly. Alterations in HSP27 may give early evidence for intracellular differences in aortic aneurysm of patients with BAV and TAV. Whether HSP27 and the defined phosphoproteins have a specific role in BAV associated aortic dilatation remains to be elucidated.

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