Crosstalk Between MASLD (Metabolically Associated Steatotic Liver Disease) and Heart Failure with Preserved Ejection Fraction (HFpEF)
Summary
This project aims to understand HFpEF in the context of hepatic metabolic disorders. We hypothesise that metabolic-associated steatotic liver disease (MASLD) contributes to HFpEF through metabolic and inflammatory interactions between the liver and heart.
Project aims
The project has three aims:
- Characterizing morphological and functional changes in cardiac tissue under MASLD conditions,
- Investigating the impact of liver-derived factors on cardiac function, and
- Exploring therapeutic interventions to mitigate HFpEF linked to MASLD.
We will use rodent models of MASLD and HFpEF, employing the L-NAME model and a high-fat/fructose diet, along with stem cell-derived cardiomyocyte (CM) models. Cardiac tissue morphology and gene expression will be assessed using histology, immunohistochemistry, and RNA sequencing.
The cardiac function will be evaluated in vivo using Echo-MRI and in vitro using primary cardiomyocytes from MASLD and control rodents, co-cultured to model liver-heart interactions. Functional assays will include oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyzer and calcium fluxes with the Opera Phenix Plus High-Content Screening System.
We aim to integrate data from -omics (RNAseq, proteomics, and phenomics) to identify potential mediators of MASLD-induced HFpEF. Promising proteins/metabolites will be tested in adult mice, assessing both acute and chronic effects.
This project is refined through collaboration with Dr. Ana Vujic at the University of Cambridge and ongoing collaboration with Graham Belfield at AstraZeneca (Director NGS & Transcriptomics) on MASLD molecular mechanisms. Both male and female mice will be included.
Contact details
Professor Antonio Vidal-Puig - ajv22@cam.ac.uk
Opportunities
This project is open to applicants who want to do a:
- PhD