Beneficial Effects of LOX‐1 Inhibition on Brain Endothelial Proinflammatory Mediators and Barrier Proteins Following OxLDL Plus Acute Ischemic Injury

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Wendt, Trevor S., Gonzales, Rayna J.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R5618

Acute ischemic stroke (AIS) triggers endothelial activation and induces cerebrovascular inflammation which can result in vascular integrity loss leading to worsened stroke outcome. A clinically correlated risk factor for stroke shown to mediate vascular injury is elevated levels of oxidized low‐density lipoprotein (OxLDL). Via the lectin‐like OxLDL receptor 1 (LOX‐1), OxLDL contributes to mechanisms associated with vascular dysfunction and inflammation. The impact of OxLDL/LOX‐1 on cerebrovascular endothelial dysfunction and inflammation in the setting of AIS remains to be elucidated. The aim of this study is to investigate the effect of OxLDL via LOX‐1 on endothelial proinflammatory mediator and integral barrier protein levels during in vitro ischemic‐like conditions. We hypothesized that acute ischemic injury would increase endothelial barrier dysfunction as well as inflammation and that OxLDL would exacerbate these responses in a LOX‐1 dependent manner. Primary male human brain microvascular endothelial cells (HBMEC) were preconditioned with human OxLDL (50μg/dL; 12h) or vehicle using a serum dose reported in AIS patients. Next cells were treated with BI‐0115 (selective LOX‐1 inhibitor; 10μM) or vehicle (