Maximus Peto’s Commentary
This was a cell culture study, so its results may not be representative of what happens in aging humans, but it seems relevant. Could GO and MGO contribute to an accumulation of senescent endothelial cells during human aging, which may more-or-less permanently effect the function of the endothelium, assuming senescent cells accumulate and do not revert to quiescent (non-senescent) cells? If so, could these senescent cells be expected to be ablated with senescent cell ablation methods? Would that fix the problems that senescent endothelial cells presumably cause?
Dicarbonyls induce senescence of human vascular endothelial cells.
Mech Ageing Dev. 2017 Sep;166:24-32.
Navarrete Santos A, Jacobs K, Simm A, Glaubitz N, Horstkorte R, Hofmann B
PubMed publication date (edat): 8/7/2017
Glyoxal (GO) and Methylglyoxal (MGO) are two dicarbonyls involved in the formation of advanced glycation end products (AGEs). Endothelial cells in the vessels are in constant contact with circulating AGEs and dicarbonyls. With this project, we aimed to elucidate the effect of GO and MGO on primary human vascular endothelial cells (HVECs).
Graft material from patients with coronary heart disease was used as HVECs source. HVECs were treated with different concentrations of GO and MGO. β-Galactosidase related senescence activity and cell morphology were analyzed. AGEs as well as p21 protein expression, glyoxalase-I expression and oxidative stress were detected.
We here provide evidences that GO and MGO induce senescence in primary HVECs. Mechanistically GO and MGO induce senescence by increasing the ROS production, the expression of p21, the accumulation of AGEs and the arrest of HVECs in the G2 cell cycle phase. Aminoguanidine – a dicarbonyl scavenger – abrogated the effect of GO and MGO.
Our data are relevant as they suggest that in diseases with elevated dicarbonyl concentrations, deleterious effects on the endothelium and the development of vascular dysfunction have to be expected. On the other hand, treatment of patients with dicarbonyl scavenger could prevent this.