Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain

Subhasis Chatterjee, Lawrence T. Bish, Vasant Jayasankar, Allan S. Stewart, Y. Joseph Woo, Michael T. Crow, Timothy J. Gardner, H. Lee Sweeney, G. Alexander Patterson, Christopher A. Caldarone, Ralph J. Damiano

Research output: Contribution to journalArticle

Abstract

Objectives: Apoptosis caused by acute ischemia and subsequent ventricular remodeling is implicated as a mediator of heart failure. This study was designed to assess the efficacy of in vivo viral gene transfer of the antiapoptotic factor apoptosis repressor with caspase recruitment domain to block apoptosis and preserve ventricular geometry and function. Methods: In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adenovirus-apoptosis repressor with caspase recruitment domain was compared with empty vector adenovirus-null controls. Cardiac function was assessed by echocardiography and sonomicrometry of the border zone compared with the normal left ventricle. Animals were killed at 6 weeks with measurements of ventricular geometry and apoptosis. Results: Animals with the apoptosis repressor with caspase recruitment domain (ARC group) maintained higher ejection fractions at 4 and 6 weeks, and sonomicrometry demonstrated greater protection of border zone fractional shortening at 6 weeks compared with the control group. The ARC group maintained superior preservation of left ventricular geometry with less ventricular dilation and wall thinning. Finally, there was reduced apoptosis in the rabbits treated with apoptosis repressor with caspase recruitment domain compared with the controls. Conclusions: Gene transfer of apoptosis repressor with caspase recruitment domain preserves left ventricular function after ischemia. The benefit at 6 weeks is postulated to result from an apoptosis repressor with caspase recruitment domain-mediated reduction in apoptosis and ventricular remodeling. Adenovirus-apoptosis repressor with caspase recruitment domain administration offers a potential strategy after myocardial ischemia to protect the heart from late postischemic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)1461-1469
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume125
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Viral Genes
Cardiomyopathies
Apoptosis
Adenoviridae
AIDS-Related Complex
Ventricular Remodeling
Ischemia
Caspase Activation and Recruitment Domain
Rabbits
Transfer Factor
Ventricular Function
Left Ventricular Function
Reperfusion
Heart Ventricles
Myocardial Ischemia
Echocardiography
Dilatation
Heart Failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain. / Chatterjee, Subhasis; Bish, Lawrence T.; Jayasankar, Vasant; Stewart, Allan S.; Woo, Y. Joseph; Crow, Michael T.; Gardner, Timothy J.; Sweeney, H. Lee; Patterson, G. Alexander; Caldarone, Christopher A.; Damiano, Ralph J.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 125, No. 6, 01.06.2003, p. 1461-1469.

Research output: Contribution to journalArticle

Chatterjee, S, Bish, LT, Jayasankar, V, Stewart, AS, Woo, YJ, Crow, MT, Gardner, TJ, Sweeney, HL, Patterson, GA, Caldarone, CA & Damiano, RJ 2003, 'Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain', Journal of Thoracic and Cardiovascular Surgery, vol. 125, no. 6, pp. 1461-1469. https://doi.org/10.1016/S0022-5223(02)73229-7
Chatterjee, Subhasis ; Bish, Lawrence T. ; Jayasankar, Vasant ; Stewart, Allan S. ; Woo, Y. Joseph ; Crow, Michael T. ; Gardner, Timothy J. ; Sweeney, H. Lee ; Patterson, G. Alexander ; Caldarone, Christopher A. ; Damiano, Ralph J. / Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain. In: Journal of Thoracic and Cardiovascular Surgery. 2003 ; Vol. 125, No. 6. pp. 1461-1469.
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AU - Jayasankar, Vasant

AU - Stewart, Allan S.

AU - Woo, Y. Joseph

AU - Crow, Michael T.

AU - Gardner, Timothy J.

AU - Sweeney, H. Lee

AU - Patterson, G. Alexander

AU - Caldarone, Christopher A.

AU - Damiano, Ralph J.

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