Epigenetic-sensitive mechanisms, coding/non-coding genes, and paracrine mediators in multipotent stem cells from epicardial fat

Obiettivi del progetto

Epicardial adipose tissue (EAT), the fat depot that directly surrounds the heart and is contained beneath the pericardium, has acquired an exponential scientific interest in the last decade. EAT also represents a source of adipose stem cells (ASCs), characterized by pluripotent differentiation capacity which deserves further investigation. Remarkably, epicardial ASCs (e-ASCs) have been reported to have a higher cardiomyogenic potential as compared to pericardial and omental ASCs subtypes and to have marked proangiogenic and immunomodulatory effects. However, little is known about the e-ASCs contribution to the milieu affecting cardiac function or to the endogenous repair process in the ischemic milieu associated with CHD. However, detailed studies aimed to investigate the epigenetic regulation of e-ASCs differentiative and paracrine effects are still lacking. The present project aims to expand current limited knowledge on e-ASC methylation and gene expression profiles in comparison to ASCs derived from subcutaneous or visceral fat depots. We intend to perform an extensive characterization of their differentiation potential and paracrine effects and to analyze their gene modulation in the context of CHD by means of DNA methylome and transcriptional analyses. The computational integration of methylation and expression data will allow us to draw a network of epigenetic changes that control the expression/repression of specific genes related to e-ASC biology and CHD pathogenesis, and to identify novel molecules for targeted experimental validation. Concurrently, we will investigate the role of adipogenic pathways involved in EAT formation and remodeling by epicardial progenitor cells (EPDCs) and their epigenetic regulation in vitro on the mouse and human cells and in vivo on murine models, searching for novel strategies aimed to prevent or delay EAT enlargement, dysfunction, and inflammation related to CHD onset and progression. The correlation between molecular/omics data and clinical phenotype of CHD patients will allow us to find out epigenetic-sensitive biomarkers that will be further validated through liquid-based assays on CHD patient serum samples.

Data di inizio e fine

Responsabile del progetto

Massimo Chello, Antonio Nenna

Istituzione coordinatrice del progetto

Università degli Studi di ROMA "La Sapienza

Università degli Studi di ROMA "Tor Vergata"

Altre Istituzioni coinvolte

• UCBM

Fonte/i di finanziamento