( D) Monocytes were embedded in fibrinogen-deficient plasma that was reconstituted with increasing concentrations of fibrinogen (right).
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( C) Monocytes were embedded in plasma clots that were generated from normal plasma or fibrinogen-deficient plasma (left). ( B) Monocytes were embedded into plasma fibrin clots formed in the presence of GPRP, a fibrin polymerization inhibitor or vehicle (water). Monocytes were then incubated with plasma clots or in residual serum. After two hours, serum was removed from the plasma clots by centrifuging the sample at 12,000 x g for 20 minutes. ( A) Purified, cell-free plasma clots were triggered with recombinant tissue factor and calcium. Dampening of inflammatory gene expression by timely clot lysis may contribute to the clinically proven efficacy of fibrinolytic drug treatment within hours of stroke onset.įibrin fibrinogen inflammation monocytes thrombin. These findings demonstrate that clots are potent inducers of monocyte gene expression and that timely fibrinolysis attenuates inflammatory responses, specifically IL-8 and MCP-1. Consistent with these in vitro models, monocytes embedded in unresolved thrombi from patients undergoing thrombectomy stained positively for IL-8 and MCP-1. Fibrinolysis initiated shortly after plasma clot formation (ie, 1-2 hours) reduced the synthesis of IL-8 and MCP-1, whereas delayed fibrinolysis was far less effective. Upregulation of IL-8 and MCP-1 occurred in a thrombin-independent but fibrin-dependent manner. Clotted plasma also increased expression of IL-8 and MCP-1, which far exceeded responses observed in lipopolysaccharide-stimulated monocytes. Numerous mRNAs were differentially expressed by monocytes embedded in clots compared with unclotted controls, and IL-8 (interleukin 8) and MCP-1 (monocyte chemoattractant protein-1) were among the upregulated transcripts in both models. We performed next-generation RNA sequencing on monocytes extracted from whole blood clots and using a purified plasma clot system. Determine whether clot formation and lysis regulates the expression of human monocyte-derived genes that modulate vascular diseases.
![gene expression c artoon gene expression c artoon](https://c8.alamy.com/comp/J73AJN/a-cartoon-lion-with-an-angry-expression-J73AJN.jpg)
The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown. In the end, Deitch concedes that the whole debate about what is and what isn’t animation may be little more than a trivial technicality because a film’s worth is not rooted in its technique: “We may simply have to give up trying to categorize films by their technical process of production, which will surely be more and more a mixed bag of tricks, and simply judge them as films.Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. “We are graphic artists, and graphic art can be wildly anything.” Beowulf is not even mildly anything as far as animation art goes. “We animators can animate absolutely anything we can imagine,” he writes. Deitch’s primary complaint is that while the type of work on display in Beowulf is technically qualifiable as animation, it is not a creative use of the medium. Serving as an appropriate complement to this earlier piece on Cartoon Brew, animation legend Gene Deitch has written a piece for Animation World Magazine entitled “Yes, But is It Animation?” in which he uses Beowulf as a jumping point for his thoughts on motion and performance capture.