Congestive heart failure is a widespread disease for which there is no other cure than heart transplantation. The aim of this project we is to create a conditional transgenic animal model of gene therapy for heart failure. Several evidences suggest that continuous desensitization of adrenergic receptors in hypertrophic hearts may be a primary factor in initiating the pathological changes that lead to overt heart failure (1,2,3,4). To challenge this hypothesis we generated a mouse strain in which a transgene encoding for desensitization-resistant beta adrenergic receptors can be switched on in response to withdrawal of doxycyclin from diet (5). In this animal model, following experimentally-induced heart failure, it will be possible to study whether the transient expression of the modified receptor at varius stages of the pathological progression can prevent or rescue the heart from failure. This study has two main aims. First, to assess if receptor desensitization has a critical role in starting the pathological changes that destroy the cardiac muscle during the disease. Second, it will explore a novel possible strategy of therapy for heart failure based on the introduction in myocardiocytes of genetically engineered adrenergic receptors.
CONDITIONAL TRANSGENIC MOUSE WITH DESENSITIZATION-RESISTANT BETA ADRENERGIC RECEPTOR AS A MODEL OF GENE THERAPY FOR HEART FAILURE
Mattei E;
2001
Abstract
Congestive heart failure is a widespread disease for which there is no other cure than heart transplantation. The aim of this project we is to create a conditional transgenic animal model of gene therapy for heart failure. Several evidences suggest that continuous desensitization of adrenergic receptors in hypertrophic hearts may be a primary factor in initiating the pathological changes that lead to overt heart failure (1,2,3,4). To challenge this hypothesis we generated a mouse strain in which a transgene encoding for desensitization-resistant beta adrenergic receptors can be switched on in response to withdrawal of doxycyclin from diet (5). In this animal model, following experimentally-induced heart failure, it will be possible to study whether the transient expression of the modified receptor at varius stages of the pathological progression can prevent or rescue the heart from failure. This study has two main aims. First, to assess if receptor desensitization has a critical role in starting the pathological changes that destroy the cardiac muscle during the disease. Second, it will explore a novel possible strategy of therapy for heart failure based on the introduction in myocardiocytes of genetically engineered adrenergic receptors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
