Diabetes mellitus is hallmarked by accelerated atherosclerosis, a major cause of mortality
among patients with diabetes. Efficient therapies for diabetes-associated atherosclerosis are absent.
Accelerated atherosclerosis in diabetic patients is associated with reduced endothelial thrombomodulin
(TM) expression and impaired activated protein C (aPC) generation. Here, we directly
compared the effects of high glucose and oxidized LDL, revealing that high glucose induced more
pronounced responses in regard to maladaptive unfolded protein response (UPR), senescence, and
vascular endothelial cell barrier disruption. Ex vivo, diabetic ApoE mice displayed increased
levels of senescence and UPR markers within atherosclerotic lesions compared with nondiabetic
ApoE mice. Activated protein C pretreatment maintained barrier permeability and prevented
glucose-induced expression of senescence and UPR markers in vitro. These data suggest that high
glucose-induced maladaptive UPR and associated senescence promote vascular endothelial cell
dysfunction, which—however—can be reversed by aPC. Taken together, current data suggest that
reversal of glucose-induced vascular endothelial cell dysfunction is feasible.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87858 |
| Date | 02 November 2023 |
| Creators | Fatima, Sameen, Ambreen, Saira, Mathew, Akash, Elwakiel, Ahmed, Gupta, Anubhuti, Singh, Kunal, Krishnan, Shruthi, Rana, Rajiv, Khawaja, Hamzah, Gupta, Dheerendra, Manoharan, Jayakumar, Besler, Christian, Laufs, Ulrich, Kohli, Shrey, Isermann, Berend, Shahzad, Khurrum |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2786 |
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