Modeling diabetes with pluripotent stemcells

Title	Modeling diabetes with pluripotent stemcells
Acronym	MODIA
Website	NA
Start date	2018-09-01
End date	2021-08-01
Sponsor	Gustave Roussy
Institution	University Medical Center Groningen

Associated cell lines

Project Description

Diabetes mellitus type II (DM) not only is an important risk factor for developing heart failure (HF) but also increases the risks of HF mortality and hospitalization in patients with established HF. The pathophysiological role of DM in HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are potentially different. In patients with HFrEF, DM is associated with more eccentric cardiac hypertrophy, while in patients with HFpEF, DM is associated with a concentric cardiac hypertrophy1. On a cellular level, early evidence suggests that in the diabetic HFpEF phenotype, collagen and advanced glycation end-products (AGEs) deposition are increased. In contrast, cardiomyocytes in patients with the diabetic HFrEF phenotype show an overall loss of sarcomeres2. A greater understanding of the underlying pathophysiologic mechanisms that lead to the development of both HF phenotypes when DM occurs is an important unmet need. This is mainly due to the complex network of factors involved. Bioinformatics and network analyses can help us identify relevant multifactorial pathological mechanisms by recognizing key regulatory disease pathways associated with DM in HF and allowing comparisons between HFrEF and HFpEF phenotypes. A deeper understanding of the pathophysiology of HF when it co-occurs with DM will lead to the recognition of new molecular targets and establishment of novel personalized treatments. The overall aim of this proposal is to elucidate the differences between heart failure patients with and without diabetes. We will then investigate mechanistic implications of patient specific treatment targets in in-vitro.