Late Breaking Science posters

Abstract

Background: Endothelial cells (ECs) are plastic cells that switch between growth/senescence states: they divide and migrate upon proangiogenic stimulation and become senescence in response to various physiologic stresses. Cellular senescence is associated with cellular dysfunction and has been shown to occur in vivo in age-related cardiovascular diseases. Purpose: Adjusting endothelial metabolism to the growth state is central to normal cellular function, yet it is poorly understood at the molecular level. We report that the Aldehyde Dehydrogenase (ALDH)2 couples metabolic and senescence in ECs. Methods: Human umbilical vein endothelial cells were cultured until senescence in the presence or absence of ALDH2 inhibitor, daidzin at doses of 10 mM. Senescent cells were compared with nonsenescent cells. Cell proliferation, sprouting and miRNAs expressions were studied. Results: Pharmacological inhibition of ALDH-2 in EC induces a marked upregulation of senescent markers, such as ALDH1A3, p16, and p21 that interfere with sprouting capability and proliferation in vitro assays. Further, senescent EC show a reduced cumulative population doubling, b-galactosidase accumulation, down-regulation of telomerase reverse transcriptase mRNA expression, decreased telomerase activity. We find that ALDH2 decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, ALDH2 regulates miRNAs involved in cell senescence and reduces signalling by pro-angiogenic factors, including VEGF. Modulation of miRNAs expression by mimic or antagomir in ALDH2-expressing endothelium normalizes EC growth and branching behaviour. Conclusion: Our findings identify ALDH2 as a critical metabolic checkpoint during endothelial growth and senescence.

Cite this paper

@inproceedings{Donnini2016LateBS, title={Late Breaking Science posters}, author={Sandra Donnini and Erika Terzuoli and Federica Finetti and Marina Ziche and Carla Giordano and Laura Raimondi and Caterina Miceli and Stefania Rigacci and Chiara Nediani}, year={2016} }