ALTERATIONS IN CONTRACTION AND RELAXATION PROPERTIES OF CARDIAC SARCOMERES IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY (HCM): STUDY AT SINGLE MYOFIBRIL LEVEL

Familial hypertrophic cardiomyopathy (HCM) is by far the most frequent and life-threatening hereditary cardiopathy. It is generally diagnosed after puberty, sometimes following a dramatic event as syncope and sudden death that occurs in 2-3% of the individuals (4-6% in childish or adolescence). Recent advancement in human genetics has allowed identifying the mutant genes for at least nine forms of HCM: they all encode for proteins involved in the basic mechanisms of muscle contraction as myosins, tropomyosins, etc., proteins which assemble in a structure called 'sarcomere'. In fact, hypertrophy (i.e., increase of ventricular wall thickness from which the illness definition) represents just heart adaptation. We know now that the true illness resides in the incapability of the cardiac muscle to contract efficiently: with the time, the cardiac muscle reacts to the inherited defect by modifying dimensions and structure. The hypertrophic progress, however, doesn’t counterbalance the initial deficit; rather, the progression of the illness involves an inexorable worsening of patients' general conditions and the risk of sudden death. Therapeutic approaches, either medical or surgical, to the treatment of the HCM substantially aim to improve the quality of life of the patient and to reduce risk for fatal arrhythmias, but a treatment against the illness cause doesn't exist. Actually, if one wondered what's wrong in the contractile apparatus of that patient, and therefore what would hypothetically be adjusted for recovering it, there wouldn't be an answer, if not indirect. Nobody has ever measured how cardiac sarcomeres of a HCM patient work in comparison to a healthy person, and if replacing or suppressing the defective protein (i.e., the potential goal of a gene therapy) their normal function can be restored. This is the main purpose of the present project, through an innovative technique just transferred from the animal to human cardiac biopsies.