313 Circulating antibodies to heat shock protein 65 in patients with heart failure

Increased production of Heat Shock Proteins (HSP) is observed in the cells, including cardiomyocytes, to protect themselves against stress stimuli. These proteins, that appear to be involved in repair processes and have a number of cellular functions such as protein assembly and folding and transport crossing intracellular membranes, are also involved in cardiovascular diseases. Increased circulating levels of Hsp 60 as well as increased titers of antibodies against mycobacterial Hsp 65 have been found to be associated with different cardiovascular diseases. Chronic heart failure (CHF) is a situation of chronic stress, characterized by the presence of factors, such as cytokines, able to increase the HSP. The concentrations of HSP in the failing hearts are increased with respect to nonfailing hearts, both in humans and in animal models. However data about the presence of HSP or their antibodies in peripheral circulation in this situation are so far lacking. For this, circulating anti-mycobacterial 65kDa protein antibodies were evaluated in 78 patients with CHF (ejection fraction, LVEF, 33.6 ± 0.87, 54 in I-II NYHA class and 24 in III-IV class) and in 27 healthy subjects as control, by using an ELISA method. Scalar dilutions (from 1:100 to 1:1600) of each serum sample were assayed. Scalar dilution of a negative sample and of 2 different positive samples were also evaluated in each run for quality control purpose. Antibodies to Hsp 65 were found in the 70% of the patients with CHF (titres ranged from 1:100 to 1:1600) and in the 68% of controls (titres ranged from 1:100 to 1:400). Mean (±SEM) antibody titres resulted: 222 ± 32 in controls, 304 ± 43 and 408 ± 55 in CHF patients in I-II and III-IV NYHA class, respectively (p=0.035 III-IV class vs. controls by Fisher test after ANOVA). No significant association between antibody titre and degree of myocardial dysfunction, as assessed by LVEF, was found. The positive correlation of the anti-Hsp 65 titres with clinical severity (NYHA class) suggests a role for HSP in this disease, however the clinical relevance of this determination has to be assessed by the comparison with the distribution of anti-Hsp 65 antibodies in larger age- and sex-matched healthy population (whose recruitment is now in progress), as well as by the comparison with hemodynamic and biohumoral markers of CHF. 314 Heat shock protein 72 in heart failure