| http://purl.uniprot.org/citations/35014606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35014606 | http://www.w3.org/2000/01/rdf-schema#comment | "Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell (EC) gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified kallikrein-related peptidase 10 (Klk10, a secreted serine protease) as a flow-sensitive gene in mouse arterial ECs, but its role in endothelial biology and atherosclerosis was unknown. Here, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo mouse models and in vitro studies with cultured ECs. Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated Klk10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced permeability dysfunction and inflammation in human artery ECs, as determined by NFκB activation, expression of vascular cell adhesion molecule 1 and intracellular adhesion molecule 1, and monocyte adhesion. Furthermore, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of Klk10-expressing plasmids inhibited atherosclerosis in Apoe-/- mice. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques. KLK10 is a flow-sensitive endothelial protein that serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.org/dc/terms/identifier | "doi:10.7554/elife.72579"xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Kumar S."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Lee H."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Liu R."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Mihara K."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Pohl J."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Williams D."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Jo H."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "An Y."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Dai Z."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Tate E.W."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Diamandis E.P."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Bagchi P."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Kang D.W."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Hollenberg M.D."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Mahmoud M."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Baek K.I."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Mosnier L.O."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Andueza A."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Villa-Roel N."xsd:string |
| http://purl.uniprot.org/citations/35014606 | http://purl.uniprot.org/core/author | "Tamargo I."xsd:string |