Molecular and physiological alterations in murine ventricular dysfunction

Howard A. Rockman, Satoko Ono, Robert S. Ross, Larry Jones, Mohsin Karimi, Valmik Bhargava, John Ross, Kenneth R. Chien

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca2+- ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defined alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.

Original languageEnglish
Pages (from-to)2694-2698
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number7
StatePublished - Mar 29 1994

Fingerprint

Ventricular Dysfunction
Right Ventricular Dysfunction
Constriction
Pulmonary Artery
Heart Ventricles
Dilatation
Down-Regulation
Phenotype
Right Ventricular Function
Tricuspid Valve Insufficiency
Lung
Ventricular Function
Calcium-Transporting ATPases
Sarcoplasmic Reticulum
Genetic Markers
Pulmonary Hypertension
Stroke Volume
Hypertrophy
Myocardium
Proteins

Keywords

  • Ca- ATPase
  • digital angiography
  • heart failure
  • phospholamban
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Rockman, H. A., Ono, S., Ross, R. S., Jones, L., Karimi, M., Bhargava, V., ... Chien, K. R. (1994). Molecular and physiological alterations in murine ventricular dysfunction. Proceedings of the National Academy of Sciences of the United States of America, 91(7), 2694-2698.

Molecular and physiological alterations in murine ventricular dysfunction. / Rockman, Howard A.; Ono, Satoko; Ross, Robert S.; Jones, Larry; Karimi, Mohsin; Bhargava, Valmik; Ross, John; Chien, Kenneth R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 7, 29.03.1994, p. 2694-2698.

Research output: Contribution to journalArticle

Rockman, HA, Ono, S, Ross, RS, Jones, L, Karimi, M, Bhargava, V, Ross, J & Chien, KR 1994, 'Molecular and physiological alterations in murine ventricular dysfunction', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 7, pp. 2694-2698.
Rockman, Howard A. ; Ono, Satoko ; Ross, Robert S. ; Jones, Larry ; Karimi, Mohsin ; Bhargava, Valmik ; Ross, John ; Chien, Kenneth R. / Molecular and physiological alterations in murine ventricular dysfunction. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 7. pp. 2694-2698.
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