Dalla ricerca di base alla pratica clinica: Nuove prospettive terapeutiche nello scompenso cardiaco

Despite significant advances in pharmacological and clinical treatment, heart failure remains a leading cause of morbidity and mortality worldwide. G-protein coupled receptors are a wide superfamily of plasma membrane receptors which represent an important target of heart failure drug therapy. Since heart failure is characterized by the overactivity of different neurohormones, such as catecholamines and angiotensin II, responsible for several detrimental effects on the cardiovascular system, over the last decade therapeutic strategies targeting beta-adrenergic and angiotensin receptors have been developed. Despite the introduction of successful drug classes, such as beta-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors and sartans, heart failure still poses an enormous challenge, thus indicating the urgent need to develop innovative treatments that might counteract mechanisms involved in heart failure onset and progression. It is now established that a single receptor, activated by the same agonist, can elicit several different signaling pathways often resulting in opposite cellular responses, some beneficial and some detrimental. However, drugs currently used in heart failure target receptors on their extracellular domain by competing with the endogenous agonists. Thus, they can inhibit non-specifically all the receptor-related signaling pathways including those with beneficial activity whose blockade would not be desirable in heart failure. These observations stress the need for the generation of new therapeutic molecules able to target specific signaling pathways which might result in innovative therapies for cardiovascular disease.