Hypertension & Healthcare

Biography

Biography: Werner Seeger

Abstract

The lecture will summarize the progress that has been made in the treatment of pulmonary hypertension (PH) over the past two decades. Here, it will address pulmonary vasodilatory treatment concepts, with particular focus on the prostaglandin I2 – cAMP and the NO synthase - soluble guanylate cyclase – cGMP – phosphodiesterase V pathways. It will, however, point out that the abnormal inward remodeling processes underlying PH go far beyond vasomotor abnormalities, and that the development of vascular “reverse remodeling” and “regenerative” strategies represents the future challenge of PH therapy. Open issues that will be addressed in this lecture are: - The role of various growth factors and transcription factors - The role of inflammatory and immunological sequelae - The role changes in the epigenetic landscape / “epigenetic memory” underlying the vascular phenotypic switch and maintenance in PH Being challenged with increased afterload in PH, the right ventricle (RV) initially responds with “adaptive” hypertrophy, which is, however, often rapidly followed by “maladaptive” changes leading to right heart failure. Though research here is still in its infancy, topics of major future relevance to be addressed in the lecture are: - RV morphogenesis and recapitulation of morphogenetic pathways in right ventricular hypertrophy - Hypoxia and ischemia in right ventricular hypertrophy - Metabolic “switch”, mitochondrial dysfunction, and enhanced formation of reactive oxygen species in RV hypertrophy - Epigenetic changes underlying the hypertrophic response profile (adaptive, maladaptive) of the right ventricle to mechanical load