Progetto TRANSAC

  • UNIVERSITÀ DEGLI STUDI DI PADOVA - PROGETTI STRATEGICI anno 2011
  • Translation in Arrhythmogenic Cardiomyopathy: from pathobiology to molecular medicine and prevention

Arrhythmogenic cardiomyopathy (AC), previously known as arrhythmogenic right ventricular cardiomyopathy, is a major cause of premature death in the young. It occurs usually abruptly in the mode of arrhythmic cardiac sudden death (SD) due to ventricular fibrillation. AC accounts for 20-25% of SD in athletes triggered by effort. AC is an autosomal dominant mendelian genetic disease, mostly due to mutations in genes encoding desmosomal proteins. The arrhythmogenic substrate consists of fibro-fatty replacement of the ventricular myocardium which is the consequence of the repair of a genetically determined myocyte death (myocardial dystrophy). Although originally described as a specific condition of the right ventricular myocardium, there is definitive evidence that AC is a biventricular disease with common left ventricular involvement, which importantly contributes to arrhythmogenesis and disease outcome. SD is pending along the natural history of the disease and several antiarrhythmic therapies, both pharmacological and non, including implantable cardioverter defibrillator (ICD), are used to prevent the fatal outcome. A cure of the disease is not yet available.

The aims of this interdisciplinary research program, named TRANSAC (TRANSlation in Arrhythmogenic Cardiomyopathy), is to gain more insight into the cellular and molecular mechanisms, relating genes and desmosomal abnormalities to onset and progression of cell death. Special attention will be given to signaling pathways and mechano-transduction by employing animals, in vitro models, induced pluripotent stem cells (iPS)-derived cardiomyocytes as well as to the use of clinical tools (biomarkers, tissue Doppler imaging -TDI- echocardiography, contrast-enhanced cardiac magnetic resonance, CE-CMR) and of cascade genetic screening from probands to family members for early diagnosis.

Overall the main goal of the investigation is to improve the knowledge on pathophysiological mechanisms to pursue a cure of the disease and to develop clinical tools for early diagnosis and risk stratification for SD prevention.

Principal investigator

  • Prof. Gaetano Thiene (Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari)
    e-mail: gaetano.thiene@unipd.it

Partnership

  • Prof. CORRADO Domenico, Dipartimento di SCIENZE CARDIOLOGICHE,TORACICHE E VASCOLARI
  • Dott. ELVASSORE Nicola Dipartimento di INGEGNERIA INDUSTRIALE
  • Prof.ssa RAMPAZZO Alessandra, Dipartimento di BIOLOGIA ( Unità di ricerca: Genetica molecolare applicata )
    e-mail: alessandra.rampazzo@unipd.it

Keywords

  • AREA 07 - MED - Med/11 - Cardiovascular System Diseases - CARDIOMYOPATHY
  • AREA 07 - MED - Med/11 - Cardiovascular System Diseases - SUDDEN DEATH
  • AREA 07 - MED - Med/08 - Pathological Anatomy - TRANSGENIC ANIMALS
  • AREA 07 - MED - Med/08 - Pathological Anatomy - GENETIC SEQUENCING
  • AREA 06 - BIOLG - MOLECULAR GENETICS