Bcl-2-associated athanogene 5 overexpression attenuates catecholamine-induced vascular endothelial cell apoptosis

Bcl-2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine-induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertension-related endothelial cell damage. Then, western blots, enzyme-linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholamine-treated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway. Reactivation of the MAPK-ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK-ERK pathway as potential mechanisms underlying catecholamine-induced endothelial cell damage.

Automated summary

Overexpression of Bag5 can reverse catecholamine-induced endothelial cell damage by inhibiting ER stress, attenuating oxidative stress, and repressing inflammation to promote cell survival. Pathway analysis showed that the MAPK-ERK pathway controls Bag5 expression, suggesting a potential mechanism for catecholamine-induced endothelial cell damage.