Spatial control of robust transgene expression in mouse artery endothelium under ultrasound guidance

Liu, Renfa; Qu, Shuai; Xu, Yunxue; Jo, Hanjoong; Dai, Zhifei

doi:10.1038/s41392-022-01031-w

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…Interestingly, KLK10, which is a member of the KLK serine/threonine protein kinase family, lacks inherent protease activity, and its anti-inflammatory and permeability-barrier-protective functions are mediated by protease-activated receptor 1 (PAR1)-dependent and PAR2-dependent pathways 143 . Administration of recombinant KLK10 via tail vein injection or ultrasound-guided delivery of a KLK10 expression vector to the carotid endothelium prevented endothelial inflammation and atherosclerosis development in mice 143 , 144 , demonstrating the proof of principle that flow-sensitive proteins such as KLK10 could be used as novel anti-atherogenic therapeutics.…”

Section: Omics Approaches To Study Endothelial Cellsmentioning

confidence: 90%

“…Numerous flow-sensitive genes (including BMP4 , DNMT1 , KDM4B , KLF2 , KLK10 , PLPP3 , SEMA7A , THBS1 , TMX1 and ZBTB46 ), miRNAs (including miR-95a and miR-712) and lncRNAs (including MALAT1 and MANTIS ) were identified from these bulk-RNA studies and subsequently validated, as reviewed elsewhere 14 , 17 , 73 , 141 , 142 . The roles of flow-sensitive miRNAs and lncRNAs in endothelial function have been reviewed previously 143 , 144 . KLK10 (which encodes kallikrein-related peptidase 10) has been identified as one of the most flow-sensitive genes from a gene-array study using the mouse PCL model 135 .…”

Section: Omics Approaches To Study Endothelial Cellsmentioning

confidence: 99%

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Flow-induced reprogramming of endothelial cells in atherosclerosis

et al. 2023

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Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success of treatments with cholesterol-lowering drugs and drug-eluting stents, raising the need to identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved and branching arterial regions, where endothelial cells are exposed to disturbed blood flow with characteristic low-magnitude oscillatory shear stress. By contrast, straight arterial regions exposed to stable flow, which is associated with high-magnitude, unidirectional shear stress, are relatively well protected from the disease through shear-dependent, atheroprotective endothelial cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic and metabolic changes in endothelial cells through mechanosensors and mechanosignal transduction pathways. A study using single-cell RNA sequencing and chromatin accessibility analysis in a mouse model of flow-induced atherosclerosis demonstrated that disturbed flow reprogrammes arterial endothelial cells in situ from healthy phenotypes to diseased ones characterized by endothelial inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition and metabolic changes. In this Review, we discuss this emerging concept of disturbed-flow-induced reprogramming of endothelial cells (FIRE) as a potential pro-atherogenic mechanism. Defining the flow-induced mechanisms through which endothelial cells are reprogrammed to promote atherosclerosis is a crucial area of research that could lead to the identification of novel therapeutic targets to combat the high prevalence of atherosclerotic disease.

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Section: Omics Approaches To Study Endothelial Cellsmentioning

confidence: 90%

Section: Omics Approaches To Study Endothelial Cellsmentioning

confidence: 99%

Flow-induced reprogramming of endothelial cells in atherosclerosis

et al. 2023

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“…We also tested this strategy for gene therapy of atherosclerosis in a mouse model. [6] The combination of ultrasound, MBs, and AAVs represents a unique strategy to achieve imaging-guided gene delivery. AAV gene vectors are the leading platform for gene delivery due to their capability to transduce a wide range of cell types in vivo.…”

Section: Journal Ofmentioning

confidence: 99%

“…Recently, our team reported such a strategy that integrates ultrasound imaging, microbubbles (MBs), and adeno-associated virus (AAV) vectors for noninvasive spatial control of transgene expression in mouse artery. [6] In our study, a clinical diagnostic ultrasound imaging system, which is also used for clinical carotid ultrasound imaging, was used for simultaneously imaging and generating ultrasound stimuli. With color Doppler ultrasound imaging, the mouse’s carotid artery can be clearly visualized, and a region of interest can be randomly selected on the image, allowing the ultrasound to be focused on that region.…”

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confidence: 99%