Decoding the Heart, Muscle and Brain Endothelial Cell Phenotype and Transcriptome in Cardiovascular Disease


Päärahoittaja


Päärahoittajan myöntämä tuki (€)

  • 40 000,00


Rahoitusohjelma


Hankkeen aikataulu

Hankkeen aloituspäivämäärä01.05.2021

Hankkeen päättymispäivämäärä31.12.2023


Tiivistelmä

Cardiovascular diseases (CVD) constitute the number one cause of death in the Western world. Aging, obesity,
and diabetes are major risk factors for the development of CVD. Obesity and diabetes are rapidly increasing
worldwide, and the aged population is at its highest level in human history. Exercise training, in turn, is known to
provide protection against the development of CVD, but the molecular mechanisms have not been fully
elucidated. Vasculature and endothelial cells are gaining increased attention as important regulators of growth,
homeostasis and regeneration in different tissues. Through its paracrine function, dysfunctional endothelium
affects all organs, and thus has an adverse effect throughout the body. Endothelium has also a unique capability
to mediate the benefits of exercise. According to our recent discovery, aging, high-fat diet and pressure overload
increase the expression of TGF-beta and EndMT related genes, and the same pathways were repressed by
exercise. In this project, we will elucidate the effects of these CVD risk factors on heart, skeletal muscle and
brain endothelial cells using single-cell RNA sequencing. These experiments will be part of my visit to Karolinska
Institutet as a visiting scientist. There will will perform part of the experiments and do most of the bioinformatics
analyses. In the third part of the project, we will study human heart failure patients and conduct single-cell RNA
sequencing from the failing hearts. Samples from the healthy donor hearts for transplantation will be used as
controls. The human data will be compared to mouse models of heart failure using myocardial infarction and
pressure overload (TAC) models. The role and mechanism of the findings from single-cell RNA sequencing will
be studied in cell culture and animal models. Findings from these studied are expected to reveal novel
information about the pathological mechanisms in endothelial cells related to CVD and especially heart failure. It
will also provide translational tools to target endothelial cells in cardiometabolic diseases.


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Viimeisin päivitys 2024-24-01 klo 10:09