Bench to Bedside - Basic Science
Women are better
Antonio Abbate from Richmond,US gave a perfect introduction to a crescendo session. Although from epidemiological data the picture is emerging that women with CVD have a worse prognosis, he showed several pieces of evidence why females are better equipped. From mouse models and man there is proof of beneficial remodelling in pressure and volume overload and IHD favoring female adaptation. Recent clinical trials also support reduced mortality in the Charm study and upon treatment of heart failure with bisoprolol.
This was also underscored by the data presented by Vera Regitz Zagrosek Berlin Germany. In addition she confirmed previous data on the essential role of ERß in mediating the cardiac response to pressure overload. She showed interesting data for different responses in mice of both gender on aortic banding. In males, fibrosis is crucial and in females, the metabolism seems to be crucial and regulated through estrogen receptors.
Dr Richard (Montpellier France), showed fascinating data on differences between potassium and calcium currents in order to explain differences in APD and QT duration. Previous work shows the limited repolarization reserve of isolated female cardiomyocytes. Interesting results were explained where blocking Isus with FK506 made cells more susceptible for changes in calcium handling and delayed after depolarizations. The septal cells seem to be different between males and females.
A perfect example of translational medicine was given by Denise Hilfiker Kleiner. She showed evidence for a physiological hypertrophy during pregnancy and made the step to the sometimes lethal, sometimes reversible disease of post-partum cardiomyopathy. A suitable model was found in the STAT-3 deficient mice. These mice have impaired lv function after delivery and increased mortality. In the mouse, prolactin is cleaved by CathepsinD creating a cardiotoxic 16kD prolactin product. By inhibiting prolactin production in the mice with bromocryptin this process was blocked and improved function and survival. This was tested in a small clinical trial with spectacular results and 100% survival in these severly diseased young mothers.