[eng] Diabesity, the combination of diabetes and obesity and their close relationship, is often deemed
as the world’s largest epidemic. Increased adiposity has several cardiovascular consequences,
and oestrogen has been shown to have beneficial effects on the cardiovascular system; however,
its exact signalling mechanism has yet to be elucidated in many cases. Determining via which
receptor oestrogen signals in endothelial cells is of great interest, since endothelial dysfunction
is considered an initial step in atherosclerosis, and can give further insight into cardiovascular
pathologies and development of highly personalised therapies. For this reason, glucolipotoxicity
was induced in cultured human endothelial cells by treatment with high glucose and palmitate
to represent the diabetic and obese condition, and oestrogen signalling was analysed looking
specifically at responses when signalling via each receptor separately. In general, 17β-oestradiol
(E2) ameliorated endothelial dysfunction when signalling via its membrane-bound receptor
GPER; however, signalling via nuclear receptors ERα or ERβ appeared to increase expression of
markers of endothelial dysfunction, such as ICAM-1 and VCAM-1, indicating that E2’s beneficial
effects may be associated with GPER signalling. However, E2’s role in glucolipotoxicity may also
be the contrary. E2 signalling via ERα or ERβ appears to play a detrimental role, as it also
aggravated ROS production, as well as increased E-selectin expression. Altogether, this work
demonstrates that E2’s beneficial effects may be associated via GPER signalling and also
highlights the importance of exploring E2 receptors and their implication in endothelial
dysfunction.