CORDIS Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo

Programme

One of the most powerful instruments of integration is the programme of jointly executed research activities. Specifically, no investigation of the amplitude and insight of that proposed in JRPA1 has so far explored phenotypes of cardiovascular autonomic control in hypertension and correlated detailed autonomic phenotypes with genes related to sympathetic and parasympathetic activity. Although increasing evidence is accumulating from basic and laboratory studies about the role of inflammatory factors and oxidative stress in the pathogenesis of cardiovascular diseases and precipitation of events, no research project other than JRPA2 has yet addressed the problem by a pathwayomic approach, i.e. by investigating most of the known genes related to these pathways, and integrating genetic, genomic and proteomic methodologies applied in a very large number of subjects with detailed cardiovascular, inflammatory and oxidative phenotypes. JRPA3 will enlarge the information so far obtained in the EPOGH cohort to a much wider cohort with the integration of data coming from other European units, and will extend available information to an area not yet explored as the relation of renal handling of the sodium and genes regulating the kidney and sodium excretion, a powerful mechanism of hypertension. Stroke is one of the most ominous consequences of hypertension, its prevalence appears to be higher in Europe than, for instance, in the Unites States and Canada. Yet, little and confusing information is available on its genetics background, a background likely to be of importance when stroke appears before old age. The proposal of JRPB1 represents a major effort to clarify the matter by using a powerful genetic instrument as family-based studies, and concentrating on a pathwayomic approach parallel to that of JRPA2, thus providing missing information on the role of the inflammatory and oxidative stress pathways in hypertensive patients having already suffered a major consequence of hypertension, such as stroke, in comparison with less complicated hypertensives as those studied in JRPA2. Likewise JRPB2, in exploring an array of genetic mechanisms possibly interested in the transition from hypertension to renal dysfunction, will contribute to fill the gap in our current understanding of the increasing incidence of renal insufficiency in Europe. Finally, heart failure is also representing an increasing burden of disease especially in societies in which life expectation is long, like in Europe. Hypertension is one of the two major causes of heart failure, but detailed mechanisms and particularly genetic and proteomic mechanisms of transition from uncomplicated left ventricular hypertrophy to hypertension-related cardiac failure are largely unknown. JRPB3 represents a highly integrated approach to understand some of these mechanisms and also aims to find new markers of this transition and thus to provide useful and yet unavailable diagnostic tools.
The European Union On-LineAcknowledgement of support from the Sixth Framework Programme, Thematic priority1: Life sciences, genomics and biotechnology for health contract InGenious HyperCare (LSHM-CT-2006-037093)