Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model

Amir M. Sheikh, Cindy Barrett, Nestor Villamizar, Oscar Alzate, Anne Marie Valente, J. Rene Herlong, Damian Craig, Andrew Lodge, Jeffrey Lawson, Carmelo Milano, James Jaggers

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective: Right ventricular hypertrophy and subsequent dysfunction is common in patients with congenital heart defects, but the molecular mechanisms underlying change from adaptive hypertrophy to dysfunction remain elusive. We used the novel technique of proteomics to characterize protein changes in right ventricular myocardium in a neonatal model of right ventricular hypertrophy and early dysfunction. Methods: Twelve neonatal piglets were equally randomized to pulmonary artery banding (PAB group), or sham operation (thoracotomy without banding). After 4 weeks, right ventricular morphology and function were assessed in vivo using magnetic resonance imaging. Animals were humanely killed. Proteomics of right ventricular myocardium was performed. Purified right ventricular proteins were separated by 2-dimensional difference gel electrophoresis using fluorescent cyanine dyes. After gel imaging, software analysis revealed protein spots differentially expressed between the 2 groups; these spots were excised and identified by mass spectrometry. Results: On magnetic resonance imaging, animals with pulmonary artery banding demonstrated significant right ventricular hypertrophy, cavity dilatation, and mild systolic impairment (right ventricular ejection fraction 39.8% ± 15% vs 56.7% ± 10% controls; P < .05). Right ventricular free wall mass on harvest confirmed right ventricular hypertrophy. Proteomic analysis revealed 18 proteins that were significantly differentially expressed: 5 structural proteins, 6 metabolic enzymes, 2 stress proteins, and 5 miscellaneous proteins. Expression of calsarcin-1 and vinculin was increased, as were certain metabolic enzymes, although F1-ATPase β-chain and heat shock protein 70 decreased. Conclusions: This is the first study characterizing right ventricular protein changes in a large animal model specifically capturing the change from compensated to maladaptive hypertrophy. These findings can guide future work at elucidating the mechanisms in the pathophysiology of neonatal right ventricular hypertrophy and dysfunction.

Original languageEnglish (US)
Pages (from-to)1146-1153
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume137
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Right Ventricular Hypertrophy
Proteomics
Proteins
Hypertrophy
Pulmonary Artery
Myocardium
Two-Dimensional Difference Gel Electrophoresis
Magnetic Resonance Imaging
Right Ventricular Dysfunction
Vinculin
Right Ventricular Function
HSP70 Heat-Shock Proteins
Proton-Translocating ATPases
Congenital Heart Defects
Enzymes
Thoracotomy
Heat-Shock Proteins
Fluorescent Dyes
Stroke Volume
Dilatation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Right ventricular hypertrophy with early dysfunction : A proteomics study in a neonatal model. / Sheikh, Amir M.; Barrett, Cindy; Villamizar, Nestor; Alzate, Oscar; Valente, Anne Marie; Herlong, J. Rene; Craig, Damian; Lodge, Andrew; Lawson, Jeffrey; Milano, Carmelo; Jaggers, James.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 137, No. 5, 05.2009, p. 1146-1153.

Research output: Contribution to journalArticle

Sheikh, AM, Barrett, C, Villamizar, N, Alzate, O, Valente, AM, Herlong, JR, Craig, D, Lodge, A, Lawson, J, Milano, C & Jaggers, J 2009, 'Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model', Journal of Thoracic and Cardiovascular Surgery, vol. 137, no. 5, pp. 1146-1153. https://doi.org/10.1016/j.jtcvs.2008.09.013
Sheikh, Amir M. ; Barrett, Cindy ; Villamizar, Nestor ; Alzate, Oscar ; Valente, Anne Marie ; Herlong, J. Rene ; Craig, Damian ; Lodge, Andrew ; Lawson, Jeffrey ; Milano, Carmelo ; Jaggers, James. / Right ventricular hypertrophy with early dysfunction : A proteomics study in a neonatal model. In: Journal of Thoracic and Cardiovascular Surgery. 2009 ; Vol. 137, No. 5. pp. 1146-1153.
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