Ricerc@Sapienza

Many cardiovascular diseases are characterized by a hemodynamic overload applied on cardiac walls, activating biological processes that culminate in cardiac remodeling. Cardiac remodeling has an early adaptive phase defined as hypertrophy of the left ventricular that can eventually evolve in a maladaptive phase towards heart failure. In our previous studies, we demonstrated the importance of a communication between the brain and the spleen by a cholinergic-sympathetic pathway passing through the coeliac ganglion. This neural reflex is crucial for T cells acivation in the spleen and their egression towards target organ in the pre-hypertension induced by chronic Angiotensin II infusion in mice. Aim of the present project is to investigate whether the cholinergic-sympathetic connection could be implicated in the adaptive phase of cardiac remodeling before the establishment of chronic mechanisms. To outline this issue, we will use a murine model of transverse aortic coartaction (TAC) to induce cardiac remodeling for studying the involvement of the cholinergic-sympathetic pathway in the activation of adaptive immunity in the early phase of the process. This pathway will be studied by electrophysiological recordings of the sympathetic splenic nerve activity (SSNA) in mice subjected to TAC and in sham mice used as controls. Mice will recorded on the 4th day after TAC or sham procedure. Furthermore, SSNA in TAC and sham mice will be recorded before and after the procedure of coeliac vagotomy in order to investigate whether the coeliac branch of the vagus nerve is involved in the pathway that modulates the immune responses during the cardiac remodeling. The realization of these objectives together with those proposed in my postdoc project sets the basis for translational strategies that consider the brain-to-spleen pathway as a possible therapeutic target in cardiac remodeling to prevent heart failure.