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Updated: Aug 30, 2026

Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
Coxsackie-and-adenovirus receptor mRNA expression in human heart failure
1Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Background:
Adenoviral vectors are widely used as gene-transfer vehicles in experimental and clinical studies. Since virus incorporation and transfection efficacy depend to a large extent on the concentration of the coxsackie-and-adenovirus (CAR) receptor on target cells the aim of this study was to quantify the CAR-receptor concentration in various human cardiomyopathies.
Methods:
After RNA isolation from myocardial biopsies obtained during surgical procedures, cDNA was generated by reverse transcription. The relative RNA content was analyzed by quantitative PCR using glyceraldehydes-3-phosphate dehydrogenase (GAPDH) as a standard reference. The cardiomyopathies (CM) analyzed were categorized according to their etiology in dilated CM (DCM, n = 28), ischemic CM (ICM, n = 52), CM in mitral valve disease (MVCM, n = 32) and aortic valve disease (AVCM, n = 32). Data were related to non-cardiomyopathic tissue from donor hearts (non-CM, n = 64).
Results:
Compared with non-CM hearts DCM showed a 34-fold (+/-5.4) increase in CAR mRNA concentration, in ICM CAR mRNA was elevated by a factor of 12 (+/-4.3), in MVCM by 27 (+/-7) and AVCM by factor 47 (+/-9.3) (ANOVA p < 0.001). Compared with the expression in rat hearts CAR levels were found to be similar to those in human ICM.
Conclusions:
These results show that cardiomyopathies associated with heart failure transcribe substantially higher levels - on average by a factor of 30 - of CAR-mRNA than non-failing control hearts. Myocardial gene transfer using adenoviral vectors should therefore be facilitated in human cardiomyopathies and may present a promising approach for therapeutic interventions.
Insights
Cardiomyopathies significantly increase coxsackie-and-adenovirus (CAR) receptor mRNA levels, enhancing adenoviral vector gene transfer for potential heart failure therapies.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Gene Therapy
Background:
- Adenoviral vectors are common gene-transfer tools in research and clinical settings.
- Transfection efficiency relies heavily on coxsackie-and-adenovirus (CAR) receptor concentration on target cells.
Purpose of the Study:
- To quantify CAR receptor concentration in various human cardiomyopathies.
- To assess the impact of cardiomyopathy on CAR receptor expression.
Main Methods:
- Myocardial biopsies from patients with dilated CM, ischemic CM, and valve disease were analyzed.
- Quantitative PCR measured CAR mRNA levels relative to GAPDH in patient samples and donor hearts.
- CAR mRNA levels were compared across different cardiomyopathy types and to non-cardiomyopathic controls.
Main Results:
- CAR mRNA levels were substantially elevated in all analyzed cardiomyopathies compared to non-cardiomyopathic hearts.
- Dilated CM showed a 34-fold increase, ischemic CM a 12-fold increase, MVCM a 27-fold increase, and AVCM a 47-fold increase.
- CAR levels in human ischemic CM were comparable to those in rat hearts.
Conclusions:
- Cardiomyopathies significantly upregulate CAR-mRNA expression, averaging a 30-fold increase.
- Enhanced CAR receptor levels suggest improved myocardial gene transfer using adenoviral vectors in cardiomyopathies.
- This presents a promising avenue for therapeutic interventions in heart failure patients.
Related Concept Videos
Heart Failure II: Pathophysiology
Pathophysiology of Heart Failure
Heart Failure III: Clinical Manifestations
Cardiomyopathy IV: Restrictive Cardiomyopathy
Cardiomyopathy III: Hypertrophic Cardiomyopathy
Cardiomyopathy II: Dilated Cardiomyopathy

