Investigating the brain-to-spleen axis in hypertensive heart disease: dissection of the neural mechanisms driven by the subfornical organ in the brain circumventricular organs and promoting the splenic immune response recruited to the myocardium.
| Componente | Categoria |
|---|---|
| Gianluca Mennini | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Sergio Paolini | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Sara Perrotta | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group |
| Daniela Carnevale | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
| Vincenzo Esposito | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
Hypertension is one of most diffused chronic conditions worldwide, significantly contributing to the global disease burden. One of the major hypertension-associated organ damages is the progressive development of heart disease, also defined hypertensive heart disease (HTN-HD). This pathology often presents tracts of adaptive cardiac remodeling with preserved ejection fraction. This stage of the pathology reflects the cardiac adaptation to hemodynamic overload. Protracted and sustained overload however will often result in an aggravated condition in which the heart loses the contractile function, progressively evolving toward heart failure.
The mechanisms involved in this scenario are several and involve different systems, with a pivotal role played by the autonomic nervous system (ANS) and the immune system: the former is a well-known modulator of cardiac function and it is also capable of modulating the immune system itself; the latter is heavily involved in several aspect of hypertension and its associated organ damage and plays a role with different immune cells population in the cardiac remodeling process.
In this project we will investigate the role of the central nervous system in regulating the interplay established between ANS and immunity during HTN-HD. By using an experimental model of HTN-HD obtained by chronic infusion of Angiotensin II (AngII), we will analyze how brain regions enriched of AngII receptors, namely the circumventricular organs, can modulate the peripheral ANS to elicit the immune response from the spleen, which contribute to the process of cardiac remodeling.
Moreover, we will investigate the function that the Placental Growth Factor plays in coupling the neuro-immune interface in the spleen and thus its role in the cardiac remodeling. Achieving this goal of multilayer characterization of the pathways involved in heart failure, we will be able to identify new therapeutic targets for this pervasive and challenging chronic condition.