Vasculature in the hub of cardiometabolic disease and the health benefits of exercise – exploring novel therapeutic targets
Päärahoittaja
Rahoittajan antama koodi/diaarinumero: 220080
Päärahoittajan myöntämä tuki (€)
- 66 000,00
Hankkeen aikataulu
Hankkeen aloituspäivämäärä: 01.05.2022
Hankkeen päättymispäivämäärä: 30.04.2025
Tiivistelmä
Physical inactivity is among the strongest risk factors for cardiometabolic disease (CMD) together with ageing, obesity and hypertension. Although large epidemiological evidence supports the beneficial effects of exercise, comparatively little is known about the molecular mechanisms mediating the health benefits of exercise, especially in other tissues than skeletal muscle. As vasculature is essential for all tissues in human body, and endothelial cells (ECs) have recently been appreciated as active regulators of tissue function rather than only being inert conduits for blood flow, we hypothesise that ECs have a unique opportunity to mediate both detrimental effects of CMD risk factors and the health benefits of exercise across different tissues. Our recent studies indicate rapid adaptation of ECs to CMD risk factors and exercise training in the heart as well as to signals from other cell types (Hemanthakumar et al., 2021, Helle et al., 2021), but the effects on single-cell level and in other tissues are not known. With this project, we aim to reveal them.
First, we will discover how CMD and ageing affect ECs in different tissues and how exercise training modifies these responses in mouse models. We will use single-cell analyses to decipher transcriptomic changes in different cell types in various tissues, focusing on ECs and their interactions with other cell types. Second, we will mimic exercise in 2D and 3D cell culture models using electrical and mechanical stimulation. Third, to translate the findings to humans, we will study blood and tissue samples from CMD patients enrolled in a 1-year exercise intervention at the Exercise Medicine Clinic at the Central Hospital of Central Finland. In the systems biology analyses, we will combine the multi-omics data obtained from all experimental set-ups to identify molecular and metabolic mediators. Potentially, we will identify novel therapeutic targets for CMD for persons unable or unwilling to exercise.
First, we will discover how CMD and ageing affect ECs in different tissues and how exercise training modifies these responses in mouse models. We will use single-cell analyses to decipher transcriptomic changes in different cell types in various tissues, focusing on ECs and their interactions with other cell types. Second, we will mimic exercise in 2D and 3D cell culture models using electrical and mechanical stimulation. Third, to translate the findings to humans, we will study blood and tissue samples from CMD patients enrolled in a 1-year exercise intervention at the Exercise Medicine Clinic at the Central Hospital of Central Finland. In the systems biology analyses, we will combine the multi-omics data obtained from all experimental set-ups to identify molecular and metabolic mediators. Potentially, we will identify novel therapeutic targets for CMD for persons unable or unwilling to exercise.
Vastuullinen johtaja
Päävastuullinen yksikkö
Seurantakohteet
Profiloitumisalue: Fyysinen aktiivisuus eliniän aikana (Jyväskylän yliopisto JYU) PACTS; Hyvinvoinnin tutkimuksen yhteisö (Jyväskylän yliopisto JYU) JYU.Well
