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

A Sasse1, M Wallich1, Z Ding1

  • 1Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.

Abstract

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.

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