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

Publication ,  Journal Article
Sheikh, AM; Barrett, C; Villamizar, N; Alzate, O; Valente, AM; Herlong, JR; Craig, D; Lodge, A; Lawson, J; Milano, C; Jaggers, J
Published in: J Thorac Cardiovasc Surg
May 2009

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 F(1)-ATPase beta-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.

Duke Scholars

Published In

J Thorac Cardiovasc Surg

DOI

EISSN

1097-685X

Publication Date

May 2009

Volume

137

Issue

5

Start / End Page

1146 / 1153

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Right
  • Tissue and Organ Harvesting
  • Time Factors
  • Swine
  • Stroke Volume
  • Sensitivity and Specificity
  • Respiratory System
  • Reference Values
  • Random Allocation
  • Pulmonary Artery
 

Citation

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Sheikh, A. M., Barrett, C., Villamizar, N., Alzate, O., Valente, A. M., Herlong, J. R., … Jaggers, J. (2009). Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model. J Thorac Cardiovasc Surg, 137(5), 1146–1153. https://doi.org/10.1016/j.jtcvs.2008.09.013
Sheikh, Amir M., Cindy Barrett, Nestor Villamizar, Oscar Alzate, Anne Marie Valente, J Rene’ Herlong, Damian Craig, et al. “Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model.J Thorac Cardiovasc Surg 137, no. 5 (May 2009): 1146–53. https://doi.org/10.1016/j.jtcvs.2008.09.013.
Sheikh AM, Barrett C, Villamizar N, Alzate O, Valente AM, Herlong JR, et al. Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model. J Thorac Cardiovasc Surg. 2009 May;137(5):1146–53.
Sheikh, Amir M., et al. “Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model.J Thorac Cardiovasc Surg, vol. 137, no. 5, May 2009, pp. 1146–53. Pubmed, doi:10.1016/j.jtcvs.2008.09.013.
Sheikh AM, Barrett C, Villamizar N, Alzate O, Valente AM, Herlong JR, Craig D, Lodge A, Lawson J, Milano C, Jaggers J. Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model. J Thorac Cardiovasc Surg. 2009 May;137(5):1146–1153.
Journal cover image

Published In

J Thorac Cardiovasc Surg

DOI

EISSN

1097-685X

Publication Date

May 2009

Volume

137

Issue

5

Start / End Page

1146 / 1153

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Right
  • Tissue and Organ Harvesting
  • Time Factors
  • Swine
  • Stroke Volume
  • Sensitivity and Specificity
  • Respiratory System
  • Reference Values
  • Random Allocation
  • Pulmonary Artery