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- W4225972012 abstract "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." @default.
- W4225972012 created "2022-05-05" @default.
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- W4225972012 date "2022-01-11" @default.
- W4225972012 modified "2023-10-18" @default.
- W4225972012 title "Stable flow-induced expression of KLK10 inhibits endothelial inflammation and atherosclerosis" @default.
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- W4225972012 cites W1935076655 @default.
- W4225972012 cites W1936770188 @default.
- W4225972012 cites W1966833353 @default.
- W4225972012 cites W1972581901 @default.
- W4225972012 cites W1982149110 @default.
- W4225972012 cites W1983897833 @default.
- W4225972012 cites W1992841719 @default.
- W4225972012 cites W2002350611 @default.
- W4225972012 cites W2007343993 @default.
- W4225972012 cites W2011713635 @default.
- W4225972012 cites W2018440865 @default.
- W4225972012 cites W2025534439 @default.
- W4225972012 cites W2031287337 @default.
- W4225972012 cites W2042399529 @default.
- W4225972012 cites W2045168608 @default.
- W4225972012 cites W2057865864 @default.
- W4225972012 cites W2058258523 @default.
- W4225972012 cites W2069053245 @default.
- W4225972012 cites W2069858913 @default.
- W4225972012 cites W2080542131 @default.
- W4225972012 cites W2091399349 @default.
- W4225972012 cites W2096357860 @default.
- W4225972012 cites W2099875374 @default.
- W4225972012 cites W2104137937 @default.
- W4225972012 cites W2112540241 @default.
- W4225972012 cites W2115533377 @default.
- W4225972012 cites W2117184526 @default.
- W4225972012 cites W2118891188 @default.
- W4225972012 cites W2130770420 @default.
- W4225972012 cites W2149556400 @default.
- W4225972012 cites W2152613954 @default.
- W4225972012 cites W2153479733 @default.
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- W4225972012 cites W2155998628 @default.
- W4225972012 cites W2156270047 @default.
- W4225972012 cites W2157626278 @default.
- W4225972012 cites W2158238218 @default.
- W4225972012 cites W2160777008 @default.
- W4225972012 cites W2162499074 @default.
- W4225972012 cites W2194356469 @default.
- W4225972012 cites W2208426424 @default.
- W4225972012 cites W2258036483 @default.
- W4225972012 cites W2262850850 @default.
- W4225972012 cites W2310033666 @default.
- W4225972012 cites W2409544489 @default.
- W4225972012 cites W2560409429 @default.
- W4225972012 cites W2581605534 @default.
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- W4225972012 cites W322014996 @default.
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- W4225972012 doi "https://doi.org/10.7554/elife.72579" @default.
- W4225972012 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35014606" @default.
- W4225972012 hasPublicationYear "2022" @default.
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