Coxsackie-and-adenovirus receptor mRNA expression in human heart failure.

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.